ALBERT

Description: 〈p〉Publication date: February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1863, Issue 2〈/p〉 〈p〉Author(s): Mathilde Ménard, Florent Meyer, Ksenia Parkhomenko, Cédric Leuvrey, Grégory Francius, Sylvie Bégin-Colin, Damien Mertz〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Human serum albumin (HSA) nanoparticles emerge as promising carriers for drug delivery. Among challenges, one important issue is the design of HSA nanoparticles with a low mean size of ca. 50 nm and having a high drug payload. The original strategy developed here is to use sacrificial mesoporous nanosilica templates having a diameter close to 30 nm to drive the protein nanocapsule formation. This new approach ensures first an efficient high drug loading (ca. 30%) of Doxorubicin (DOX) in the porous silica by functionalizing silica with an aminosiloxane layer and then allows the one-step adsorption and the physical cross-linking of HSA by modifying the silica surface with isobutyramide (IBAM) groups. After silica template removal, homogenous DOX-loaded HSA nanocapsules (30–60 nm size) with high drug loading capacity (ca. 88%) are thus formed. Such nanocapsules are shown efficient in multicellular tumor spheroid models (MCTS) of human hepatocarcinoma cells by their significant growth inhibition with respect to controls. Such a new synthesis approach paves the way toward new protein based nanocarriers for drug delivery.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S0304416518303416-ga1.jpg" width="500" alt="Unlabelled Image" title="Unlabelled Image"〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 113〈/p〉 〈p〉Author(s): Agnieszka Swidnicka-Siergiejko, Urszula Wereszczynska-Siemiatkowska, Andrzej Siemiatkowski, Justyna Wasielica-Berger, Jacek Janica, Barbara Mroczko, Andrzej Dabrowski〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Introduction〈/h6〉 〈p〉The presence of esophageal varices in liver cirrhosis indicates clinically significant portal hypertension (PH), that results from structural and dynamic changes in the liver and systemic circulation including the activation of several fibrotic and inflammatory pathways. We assessed if interleukin-18 (IL-18) and transforming growth factor-β1 (TGF-β1) serum levels can be used as PH markers and reflect its severity.〈/p〉 〈/div〉 〈div〉 〈h6〉Material and methods〈/h6〉 〈p〉IL-18 and TGF-β1 peripheral blood levels were analyzed in 83 cirrhotic patients with esophageal varices compared to healthy individuals, in relation to MELD and Child-Pugh scores, laboratory and Doppler ultrasound parameters, and non-selective beta-blocker therapy (NSBB).〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉IL-18 concentration was significantly higher in cirrhotic patients, while TGF-β1 concentration was lower than in controls. MELD score correlated positively with IL-18 levels and negatively with TGF-β1 levels. IL-18 levels correlated positively with bilirubin, INR, ALT and AST levels, and negatively with albumin levels and erythrocyte count. TGF-β1 levels correlated positively with platelet count, leukocyte, and erythrocyte count, and negatively with bilirubin levels and prothrombin time. Moreover, significant correlations were found: between IL and 18 levels and portal, mesenteric superior, and splenic vein velocity, and between TGF-β1 levels and splenic vein diameter and spleen size. In a subgroup of patients, IL-18 levels significantly decreased after NSBB.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉The observed imbalance of peripheral IL-18 and TGF-β1 levels indicates clinically significant PH associated with the presence of esophageal varices in cirrhosis. The correlation of IL-18 levels with liver failure indicators and decrease with NSBB suggest an important role of IL-18 in disease progression and its potential use as noninvasive test for PH assessment.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Xing-Wei Xiang, Jin-Xing Xiao, Yu-Fang Zhou, Bin Zheng, Zheng-Shun Wen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The black seabream (〈em〉Sparus macrocephlus〈/em〉) is an economically pivotal aquaculture species cultured in China and Southeast Asian countries. To understand the molecular immune mechanisms underlying the response to 〈em〉Vibrio parahaemolyticus〈/em〉, a comparative gene transcription analysis were performed with utilized fresh livers of 〈em〉V. parahaemolyticus〈/em〉-immunized 〈em〉Sparus macrocephlus〈/em〉 with a control group through RNA-Seq technology. A total of 256663 contigs were obtained after excluded the low-quality sequences and assembly. The average length of contigs collected from this research is 1066.93 bp. Furthermore, blast analysis indicates 30747 contigs were annotated based on homology with matches in the NT, NR, gene, and string databases. A gene ontology analysis was employed to classify 21598 genes according to three major functional categories: molecular function, cellular component, and biological process. A total of 14470 genes were discovered in 303 KEGG pathways. RSEM and EdgeR were introduced to estimate 3841 genes significantly different expressed (False Discovery Rate〈0.001) which includes 4072 up-regulated genes and 3771 down-regulated genes. A significant enrichment analysis of these differentially expressed genes and isogenes were conducted to reveal the major immune-related pathways which refer to the toll-like receptor, complement, coagulation cascades, and chemokine signaling pathways. In addition, 92175 potential simple sequence repeats (SSRs) and 121912 candidate single nucleotide polymorphisms (SNPs) were detected and identified sequencely in the 〈em〉Sparus macrocephlus〈/em〉 liver transcriptome. This research characterized a gene expression pattern for normal and the 〈em〉V. parahaemolyticus〈/em〉 -immunized 〈em〉Sparus macrocephlus〈/em〉 for the first time and not only sheds new light on the molecular mechanisms underlying the host-〈em〉V. parahaemolyticus〈/em〉 interaction but contribute to facilitate future studies on 〈em〉Sparus macrocephlus〈/em〉 gene expression and functional genomics.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Yi-Hong Chen, Jian-Guo He〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The shrimp aquaculture industry is plagued by disease. Due to the lack of deep understanding of the relationship between innate immune mechanism and environmental adaptation mechanism, it is difficult to prevent and control the diseases of shrimp. The shrimp innate immune system has received much recent attention, and the functions of the humoral immune response and the cellular immune response have been preliminarily characterized. The role of environmental stress in shrimp disease has also been investigated recently, attempting to clarify the interactions among the innate immune response, the environmental stress response, and disease. Both the innate immune response and the environmental stress response have a complex relationship with shrimp diseases. Although these systems are important safeguards, allowing shrimp to adapt to adverse environments and resist infection, some pathogens, such as white spot syndrome virus, hijack these host systems. As shrimp lack an adaptive immune system, immunization therapy cannot be used to prevent and control shrimp disease. However, shrimp diseases can be controlled using ecological techniques. These techniques, which are based on the innate immune response and the environmental stress response, significantly reduce the impact of shrimp diseases. The object of this review is to summarize the recent research on shrimp environmental adaptation mechanisms, innate immune response mechanisms, and the relationship between these systems. We also suggest some directions for future research.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Yinnan Mu, Shimin Zhou, Ning Ding, Jingqun Ao, Xinhua Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Chemokines are a superfamily of structurally related chemotactic cytokines exerting significant roles in regulating cell migration and activation. Currently, five subgroups of fish specific CXC chemokines, named CXCL_F1-CXCL_F5, have been identified in teleost fish. However, understanding of the functions of these fish specific CXC chemokines is still limited. Here, a new member of fish specific CXC chemokines, 〈em〉Lc〈/em〉CXCL_F6, was cloned from large yellow croaker 〈em〉Larimichthys crocea〈/em〉. Its open reading frame (ORF) is 369 nucleotides long, encoding a peptide of 122 amino acids (aa). The deduced 〈em〉Lc〈/em〉CXCL_F6 protein contains a 19-aa signal peptide and a 103-aa mature polypeptide, which has four conserved cysteine residues (C〈sup〉28〈/sup〉, C〈sup〉30〈/sup〉, C〈sup〉56〈/sup〉, and C〈sup〉72〈/sup〉), as found in other known CXC chemokines. Phylogenetic analysis showed 〈em〉Lc〈/em〉CXCL_F6 formed a separate clade with sequences from other fish species, tentatively named CXCL_F6, distinct from the clades formed by fish CXCL_F1-5 and mammalian CXC chemokines. The 〈em〉Lc〈/em〉CXCL_F6 transcripts were constitutively expressed in all examined tissues and significantly up-regulated in the spleen and head kidney tissues by poly (I:C) and 〈em〉Vibrio alginolyticus〈/em〉. Its transcripts were also detected in primary head kidney leukocytes (HKLs), peripheral blood leucocytes (PBLs), and large yellow croaker head kidney (LYCK) cell line, and significantly up-regulated by poly(I:C), lipopolysaccharide (LPS), and peptidoglycan (PGN) in HKLs. Recombinant 〈em〉Lc〈/em〉CXCL_F6 protein (r〈em〉Lc〈/em〉CXCL_F6) could not only chemotactically attract monocytes/macrophages and lymphocytes from PBLs, but also enhance NO release and expression of proinflammatory cytokines (TNF-α, IL-1β, and CXCL8) in monocytes/macrophages. These results indicate that 〈em〉Lc〈/em〉CXCL_F6 plays a role in mediating the inflammatory response.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Jinghua Chen, Lu Zhang, Ning Yang, Mengyu Tian, Qiang Fu, Fenghua Tan, Chao Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Galectins are a family of galactoside-binding proteins with an affinity for β-galactosides, involved in mediating fundamental processes including development, inflammation, cell migration and apoptosis. Galectin-4 is a member of tendem-repeat galectins, plays vital roles in intestinal epithelial barrier. Here, one galectin-4 gene was captured in turbot (〈em〉Sm〈/em〉Lgals4) contains a 1197 bp open reading frame (ORF). In comparison to other species, 〈em〉Sm〈/em〉Lgals4 showed the highest similarity and identity both to large yellow croaker. The genomic structure analysis showed that 〈em〉Sm〈/em〉Lgals4 had conserved exons in the CRD domains compared to other vertebrate species. The syntenic analysis revealed that galectin-4 had the same neighboring genes across all the selected species, which suggested the synteny encompassing galectin-4 region during vertebrate evolution. Subsequently, 〈em〉Sm〈/em〉Lgals4 was widely expressed in all the examined tissues, with the highest expression level in intestine and the lowest expression level in skin. In addition, 〈em〉Sm〈/em〉Lgals4 was significantly down-regulated in intestine following both Gram-negative bacteria 〈em〉Vibrio anguillarum〈/em〉, and Gram-positive bacteria 〈em〉Streptococcus iniae〈/em〉 immersion challenge. Finally, the 〈em〉rSm〈/em〉Lgals4 showed strong binding ability to all the examined microbial ligands. Taken together, our results suggested 〈em〉Sm〈/em〉Lgals4 plays vital roles in fish intestinal immune responses against infection, but the detailed roles of galectin-4 in teleost are still lacking, further studies are needed to be carried out to characterize whether galectin-4 plays similar roles in teleost intestinal immunity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Yanxiu Mo, Yunpeng Fan, Wen Fu, Wenting Xu, Shujuan Chen, Yuanhui Wen, Shaojun Liu, Liangyue Peng, Yamei Xiao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Previous research has indicated that the small compound, SP600125, could induce polyploidy of fish cells, and has established a stable tetraploid cell line from diploid fish cells. In order to explore how fish cells maintain homeostasis under SP600125-stress 〈em〉in vitro〈/em〉, this study investigates impacts of SP600125-stress on intracellular pathways, as well as on regulation of the cellular homeostasis feedback in fish cells. Transcriptomes are obtained from the SP600125-treated cells. Compared with unigenes expressed in control group (crucial carp fin cells), a total of 2670 and 1846 unigenes are significantly upregulated and downregulated in these cells, respectively. Differentially expressed genes are found, which are involved in innate defense, inflammatory pathways and cell adhesion molecules-related pathways. The SP600125-stress enhances cell-mediated immunity, characterized by significantly increasing expression of multiple immune genes. These enhanced immune genes include the pro-inflammatory cytokines (IL-1β, TNF-ɑ, IL-6R), the adaptor signal transducers (STAT, IκBɑ), and the integrins (ɑ2β1, ɑMβ2). Furthermore, mitochondria are contributed to the cellular homeostasis regulation upon the SP600125-stress. The results show that acute inflammation is an adaptive and controlled response to the SP600125-stress, which is beneficial for alleviating toxicity by SP600125. They provide a potential way of breeding fish polyploidy induced by SP600125 in the future research.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Maciej Woźny, Kazimierz Obremski, Piotr Hliwa, Piotr Gomułka, Rafał Różyński, Paweł Wojtacha, Maciej Florczyk, Helmut Segner, Paweł Brzuzan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉To investigate the effects of feed contamination with zearalenone (ZEN) at the current European Commission (EC) guidance value (2 mg⋅kg〈sup〉−1〈/sup〉 feed) on the growth and health of rainbow trout, we performed a long-term feeding trial under aquaculture conditions. It started with the external feeding of the fish larvae, and continued for 96 weeks, at which point the fish had reached market size. To assess the growth of fish and their feeding efficiency throughout this period, the fish were regularly weighed and measured, and their feed consumption was monitored. Additionally, to investigate potential health effects, after 72 weeks of the exposure to ZEN, the fishes' blood was analyzed for major hematological and biochemical indices, and their head kidney, spleen, and liver were examined for morphological, histopathological, cytological, and molecular changes. Finally, to gain insight into the metabolism and distribution of ZEN in fish, the content of free and glucuronidated forms of ZEN and its major metabolites was measured in the intestine, liver, and muscles of the exposed fish. The feed-borne exposure of rainbow trout to ZEN at a dose of 2 mg⋅kg〈sup〉−1〈/sup〉 feed resulted in higher feeding efficiency and growth rate, most probably due to the anabolic properties of the ZEN metabolite. Importantly for the consumers of fish, despite absorption and metabolism of ZEN in the digestive system of the fish that had been exposed for 72 weeks, the residuals of ZEN were not transferred to the fishes’ muscles, which rules out a potential risk to human health related to the consumption of fish meat. However, the increased growth of fish fed with the contaminated feed may come at some cost, as the exposure to ZEN was associated with modulation of key components of the adaptive and innate immune systems. Moreover, the trunk kidney of ZEN-fed fish showed massive inflammation that was likely caused by pathogen infection. These findings raise concerns about fish health under the current recommended EC guidance values.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 30 October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine〈/p〉 〈p〉Author(s): Doris Kaltenecker, Madeleine Themanns, Kristina M. Mueller, Katrin Spirk, Tobias Suske, Olaf Merkel, Lukas Kenner, Andreia Luís, Andrey Kozlov, Johannes Haybaeck, Mathias Müller, Xiaonan Han, Richard Moriggl〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The rising prevalence of obesity came along with an increase in associated metabolic disorders in Western countries. Non-alcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of the metabolic syndrome and is linked to primary stages of liver cancer development. Growth hormone (GH) regulates various vital processes such as energy supply and cellular regeneration. In addition, GH regulates various aspects of liver physiology through activating the Janus kinase (JAK) 2- signal transducer and activator of transcription (STAT) 5 pathway. Consequently, disrupted GH - JAK2 - STAT5 signaling in the liver alters hepatic lipid metabolism and is associated with NAFLD development in humans and mouse models. Interestingly, while STAT5 as well as JAK2 deficiency correlates with hepatic lipid accumulation, recent studies suggest that these proteins have unique ambivalent functions in chronic liver disease progression and tumorigenesis. In this review, we focus on the consequences of altered GH - JAK2 - STAT5 signaling for hepatic lipid metabolism and liver cancer development with an emphasis on lessons learned from genetic knockout models.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 113〈/p〉 〈p〉Author(s): Maria Hansen, Anja C.B. Kuhlman, Ronni E. Sahl, Bo Kelly, Thomas Morville, Tine L. Dohlmann, Karoline M. Chrøis, Steen Larsen, Jørn W. Helge, Flemming Dela〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Purpose〈/h6〉 〈p〉Atherosclerosis is a major risk factor for cardiovascular disease (CVD) and is known to be an inflammatory process. Statin therapy decreases both cholesterol and inflammation and is used in primary and secondary prevention of CVD. However, a statin induced decrease of plasma concentrations of the antioxidant coenzyme Q10 (CoQ10), may prevent the patients from reaching their optimal anti-inflammatory potential. Here, we studied the anti-inflammatory effect of Simvastatin therapy and CoQ10 supplementation.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉35 patients in primary prevention with Simvastatin (40 mg/day) were randomized to receive oral CoQ10 supplementation (400 mg/d) or placebo for 8 weeks. 20 patients with hypercholesterolemia who received no cholesterol-lowering treatment was a control group. Plasma concentrations of lipids and inflammatory biomarkers (interleukin-6 (IL6); -8 (IL8); -10 (IL10), tumor necrosis factor-α (TNFα); high-sensitivity C reactive protein (hsCRP)) as well as glycated hemoglobin (HbA1c) were quantified before and after the intervention.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉No significant change in inflammatory markers or lipids was observed after CoQ10 supplementation Patients in Simvastatin therapy had significantly (P 〈 0.05) lower baseline concentration of IL6 (0.31 ± 0.03 pg/ml), IL8 (1.6 ± 0.1 pg/ml) IL10 (0.16 ± 0.02 pg/ml) and borderline (P = 0.053) lower TNFα (0.88 ± 0.05 pg/ml), but not hsCRP (1.34 ± 0.19 mg/l) compared with the control group (0.62 ± 0.08, 2.6 ± 0.2, 0.25 ± 0.01, 1.07 ± 0.09, and 1.90 ± 0.35, respectively).〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Simvastatin therapy has beneficial effects on inflammatory markers in plasma, but CoQ10 supplementation seems to have no additional potentiating effect in patients in primary prevention. In contrast, glucose homeostasis may improve with CoQ10 supplementation.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 113〈/p〉 〈p〉Author(s): I-Ta Lee, Chwan-Fwu Lin, Yu-Ling Huang, Kowit-Yu Chong, Ming-Fa Hsieh, Tse-Hung Huang, Ching-Yi Cheng〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Introduction〈/h6〉 〈p〉Resveratrol has been reported to alleviate inflammatory responses and oxidative stress in mesangial cells and in several types of renal injury in animal models. Previously, the active resveratrol derivatives from the roots of 〈em〉Vitis thunbergii〈/em〉 Sieb. & Zucc. (Vitaceae) were shown to have significant anti-platelet and anti-oxidative activities. However, the anti-inflammatory mechanisms of these resveratrol derivatives in rat mesangial cells (RMCs) have not been clarified fully.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉The protective mechanisms of resveratrol derivatives involved in tumor necrosis factor-α (TNF-α)-induced inflammatory responses were assessed by Western blot analysis, real-time PCR, and RT–PCR. The involvement of various signaling molecules in these responses was investigated using selective pharmacological inhibitors.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Nontoxic concentrations of the resveratrol derivatives significantly attenuated cytosolic phospholipase A〈sub〉2〈/sub〉 (cPLA〈sub〉2〈/sub〉) and cyclooxygenase 2 (COX-2) expression in RMCs challenged by TNF-α. These resveratrol derivatives inhibited TNF-α-activated ERK1/2 and JNK1/2 without affecting p38 phosphorylation. Next, we demonstrated that TNF-α induced NF-κB activation, translocation, and promoter activity, which was inhibited by pretreatment with resveratrol derivatives in RMCs.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉The protective mechanisms of resveratrol derivatives against TNF-α-stimulated inflammatory responses via cPLA〈sub〉2〈/sub〉/COX-2/PGE〈sub〉2〈/sub〉 inhibition was caused by the attenuation of the JNK1/2, ERK1/2, and NF-κB signaling pathways in RMCs.〈/p〉 〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S104346661830396X-ga1.jpg" width="207" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Xin Cai, Chengbin Gao, Huanhuan Song, Ning Yang, Qiang Fu, Fenghua Tan, Chao Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Cathepsin Z (CTSZ) is a lysosomal cysteine protease of the papain superfamily. It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. In this study, we reported the identification of 〈em〉Sm〈/em〉CTSZ, a CTSZ homolog from turbot (〈em〉Scophthalmus maximus〈/em〉 L.). 〈em〉Sm〈/em〉CTSZ was 317 residues in length and contains a Pept-C1 domain. In multiple species comparison, 〈em〉Sm〈/em〉CTSZ shared 65–93% overall sequence identities with the CTSZ counterparts from human, rat, and several fish species. In the phylogenetic analysis, 〈em〉Sm〈/em〉CTSZ showed the closest relationship to 〈em〉Cynoglossus semilaevis〈/em〉. The syntenic analysis revealed the similar neighboring genes of CTSZ across all the selected species, which suggested the synteny encompassing CTSZ region during vertebrate evolution. Subsequently, 〈em〉Sm〈/em〉CTSZ was constitutively expressed in various tissues, with the lowest and highest levels in brain and intestine respectively. In addition, 〈em〉Sm〈/em〉CTSZ was significantly up-regulated in intestine following both Gram-negative bacteria 〈em〉Vibrio anguillarum〈/em〉, and Gram-positive bacteria 〈em〉Streptococcus iniae〈/em〉 immersion challenge. Finally, the 〈em〉rSm〈/em〉CTSZ showed strong binding ability to all the examined microbial ligands, and the agglutination effect to different bacteria. Taken together, these results indicated 〈em〉Sm〈/em〉CTSZ could play important roles in mucosal immune response in the event of bacterial infection in teleost. However, the knowledge of CTSZ are still limited in teleost species, further studies should be carried out to better characterize its detailed roles in teleost mucosal immunity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Zhi Zhou, Zhaoqun Liu, Lingui Wang, Jian Luo, Hailang Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Giant clams are one of the most important animals in coral reef ecosystem, and its growth and reproduction are being threatened by heat stress due to global warming. In the present study, the symbiont density, the crucial enzyme activities and the transcriptome were investigated in the outer mantle of giant clam 〈em〉Tridacna crocea〈/em〉 after the acute exposure of high temperature. The density of symbiotic zooxanthellae decreased significantly during 12–24 h, with the minimum level (7.75 × 10〈sup〉5〈/sup〉 cell cm〈sup〉−2〈/sup〉, 〈em〉p〈/em〉 〈 0.05) at 12 h after heat stress. The activities of superoxide dismutase in the heat stress group was significantly lower than that in the control group at 24 h after heat stress, while no significant change in the activities of catalase was observed during the entire stress process. The activation level of caspase3 began to increase significantly at 12 h (1.22-fold, 〈em〉p〈/em〉 〈 0.05), and reached the highest level at 24 h (1.38-fold, 〈em〉p〈/em〉 〈 0.05) after heat stress. Six paired-end libraries were sequenced in two groups, including the heat stress and control group at 12 h after heat stress. Through the assembling of 187,116,632 paired-end reads with lengths of 2 × 150 bp, a total of 26,676 genes were obtained which derived from giant clam. Bioinformatics analysis revealed 47 significantly upregulated and 88 significantly downregulated genes at 12 h after the treatment. There were 12 overrepresented GO terms for significantly upregulated genes, mostly related to unfolded protein binding and ATP binding, whereas no GO term was overrepresented for significantly downregulated genes. These results collectively suggest high temperature could induce excessive oxidative stress through the repressed antioxidant ability, the apoptosis activated by the unfolded protein response, and further the collapse of the symbiosis between host and symbiont, which has been threatening the growth and reproduction of the giant clam 〈em〉T. crocea〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Zhi-qiang Du, Yue Wang, Hong-yu Ma, Xiu-li Shen, Kai Wang, Jie Du, Xiao-dong Yu, Wen-hong Fang, Xin-cang Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Crustins play important roles in defending against bacteria in the innate immunity system of crustaceans. In present study, we identified a crustin gene in 〈em〉Scylla paramamosain〈/em〉, which was named as 〈em〉SpCrus6〈/em〉. The ORF of 〈em〉Sp〈/em〉Crus6 possessed a signal peptide sequence (SPS) at the N-terminus and a WAP domain at the C-terminus. And there were 5 Proline residues, 5 Glycine and 4 Cysteine residues between SPS and WAP domain in 〈em〉Sp〈/em〉Crus6. These features indicated that 〈em〉Sp〈/em〉Crus6 was a new member of crustin family. The 〈em〉SpCrus6〈/em〉 mRNA transcripts were up-regulated obviously after bacteria or virus challenge. These changes showed that 〈em〉SpCrus6〈/em〉 was involved in the antimicrobial and antiviral responses of 〈em〉Scylla paramamosain〈/em〉. Recombinant 〈em〉Sp〈/em〉Crus6 (r〈em〉Sp〈/em〉Crus6) showed strong inhibitory abilities against Gram-positive bacteria (〈em〉Bacillus megaterium〈/em〉, 〈em〉Staphylococcus aureus〈/em〉, and 〈em〉Bacillus subtilis〈/em〉). But the inhibitory abilities against four Gram-negative bacteria (〈em〉Vibrio parahemolyticus〈/em〉, 〈em〉Vibrio alginolyticus〈/em〉, 〈em〉Vibrio harveyi〈/em〉 and 〈em〉Escherichia coli〈/em〉) and two fungi (〈em〉Pichia pastoris〈/em〉 and 〈em〉Candida albicans〈/em〉) were not strong enough. Besides, r〈em〉Sp〈/em〉Crus6 could strongly bind to two Gram-positive bacteria (〈em〉B〈/em〉. 〈em〉subtilis〈/em〉 and 〈em〉B〈/em〉. 〈em〉megaterium〈/em〉) and three Gram-negative bacteria (〈em〉V〈/em〉. 〈em〉alginolyticus〈/em〉, 〈em〉V〈/em〉. 〈em〉parahemolyticus〈/em〉, and 〈em〉V〈/em〉. 〈em〉harveyi〈/em〉). And the binding levels to 〈em〉S. aureus〈/em〉 and two fungi (〈em〉P〈/em〉. 〈em〉pastoris〈/em〉 and 〈em〉C〈/em〉. 〈em〉albicans〈/em〉) were weak. The polysaccharides binding assays’ results showed r〈em〉Sp〈/em〉Crus6 had superior binding activities to LPS, LTA, PGN and 〈em〉β〈/em〉-glucan. Through agglutinating assays, we found r〈em〉Sp〈/em〉Crus6 could agglutinate well three Gram-positive bacteria (〈em〉S〈/em〉. 〈em〉aureus〈/em〉, 〈em〉B〈/em〉. 〈em〉subtilis〈/em〉 and 〈em〉B〈/em〉. 〈em〉megaterium〈/em〉). And the agglutinating activities to Gram-negative bacteria and fungi were not found. In the aspect of antiviral functions, r〈em〉Sp〈/em〉Crus6 could bind specifically to the recombinant envelop protein 26 (rVP26) of white spot syndrome virus (WSSV) but not to recombinant envelop protein 28 (rVP28), whereas GST protein could not bind to rVP26 or rVP28. Besides, r〈em〉Sp〈/em〉Crus6 could suppress WSSV reproduction to some extent. Taken together, 〈em〉Sp〈/em〉Crus6 was a multifunctional immunity effector in the innate immunity defending response of 〈em〉S〈/em〉. 〈em〉paramamosain〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Yunkun Li, Jiayu Wu, Dong Li, Anqi Huang, Guixian Bu, Fengyan Meng, Fanli Kong, Xiaohan Cao, Xingfa Han, Xiaofu Pan, Wei Fan, Shiyong Yang, Xianyin Zeng, Xiaogang Du〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Schizothorax prenanti〈/em〉 (〈em〉S. prenanti〈/em〉), an important species of economical fish in Southwest China, is susceptible to 〈em〉Aeromonas hydrophila〈/em〉 (Ah). To understand the immune response to Ah, the transcriptome profiling of spleen of 〈em〉S. prenanti〈/em〉 was analyzed after Ah infection. A total of 6, 213 different expression genes (DEGs) were obtained, including 3, 066 up-regulated DEGs and 3, 147 down-regulated DEGs. These DEGs were annotated by KEGG and GO databases, so that the immune-related DEGs (IRDs) can be identified and classified. Then, the interesting IRDs were screened to build heat map, and the reliability of the transcriptome data was validated by qPCR. In order to clarify the mechanism of signal transduction in the anti-bacterial immunity, the signaling pathway initiated by TLRs was predicted. In this pathway, TLR25 and TLR5 mediate the NF-κB and AP-1 signals via MyD88-dependent pathway. Meanwhile, the type I IFN (IFNα/β) induced by IRF1 and IRF3/7 may play an important role in the anti-bacterial immunity. In conclusion, this study preliminarily provides insights into the mechanism of signal transduction after Ah infection in 〈em〉S. prenanti〈/em〉, which contributes to exploring the complex anti-bacterial immunity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Hongye Jiang, Qing Bian, Weiwei Zeng, Pengli Ren, Hengchang Sun, Zhipeng Lin, Zeli Tang, Xinyi Zhou, Qing Wang, Yingying Wang, Yensheng Wang, Mei X. Wu, Xuerong Li, Xinbing Yu, Yan Huang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Grass carp (〈em〉Ctenopharyngodon idellus〈/em〉) hemorrhagic disease (GCHD), caused by grass carp reovirus (GCRV), has given rise to an enormous loss in grass carp industry during the past years. Up to date, vaccination remained to be the most effective way to protect grass carp from GCHD. Oral vaccination is of major interest due to its advantages of noninvasive, time-saving, and easily-operated. The introduction of oral vaccination has profound impact on aquaculture industry because of its feasibility of extensive application for fish in various size and age. However, the main challenge in developing oral vaccine is that antigens are easily degraded and are easy to induce tolerance. 〈em〉Bacillus subtilis〈/em〉 (〈em〉B. subtilis〈/em〉) spores would be an ideal oral vaccine delivery system for their robust specialty, gene operability, safety and adjuvant property. VP4 protein is the major outer capsid protein encoded by GCRV segment 6 (S6), which plays an important role in viral invasion and replication. In this study, we used 〈em〉B. subtilis〈/em〉 spores as the oral delivery system and successfully constructed the 〈em〉B. subtilis〈/em〉 CotC-VP4 recombinant spores (CotC-VP4 spores) to evaluate its protective efficacy in grass carp. Grass carp orally immunized with CotC-VP4 spores showed a survival rate of 57% and the relative percent survival (RPS) of 47% after the viral challenge. Further, the specific IgM levels in serum and the specific IgZ levels in intestinal mucus were significantly higher in the CotC-VP4 group than those in the Naive group. The immune-related genes including three innate immune-related genes (IL-4/13A, IL-4/13B, CSF1R), four adaptive immune-related genes (BAFF, CD4L, MHC-II, CD8), three inflammation-related genes (IL-1β, TNF-α, TGF-β) and interferon type I (IFN-I) related signaling pathway genes were significantly up-regulated in the CotC-VP4 group. The study demonstrated that the CotC-VP4 spores produced protection in grass carp against GCRV infection, and triggered both innate and adaptive immunity post oral immunization. This work highlighted that 〈em〉Bacillus subtilis〈/em〉 spores were powerful platforms for oral vaccine delivery, and the combination of 〈em〉Bacillus subtilis〈/em〉 spores with GCRV VP4 protein was a promising oral vaccine.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: February 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Biochimica et Biophysica Acta (BBA) - General Subjects, Volume 1863, Issue 2〈/p〉 〈p〉Author(s): Priyadarshini Balaraman, Erika Plettner〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The camphor-degrading microorganism, 〈em〉Pseudomonas putida〈/em〉 strain ATCC 17453, is an aerobic, gram-negative soil bacterium that uses camphor as its sole carbon and energy source. The genes responsible for the catabolic degradation of camphor are encoded on the extra-chromosomal CAM plasmid. A monooxygenase, cytochrome P450〈sub〉cam〈/sub〉, mediates hydroxylation of camphor to 5-〈em〉exo〈/em〉-hydroxycamphor as the first and committed step in the camphor degradation pathway, requiring a dioxygen molecule (O〈sub〉2〈/sub〉) from air. Under low O〈sub〉2〈/sub〉 levels, P450〈sub〉cam〈/sub〉 catalyzes the production of borneol 〈em〉via〈/em〉 an unusual reduction reaction. We have previously shown that borneol downregulates the expression of P450〈sub〉cam〈/sub〉. To understand the function of P450〈sub〉cam〈/sub〉 and the consequences of down-regulation by borneol under low O〈sub〉2〈/sub〉 conditions, we have studied chemotaxis of camphor induced and non-induced 〈em〉P. putida〈/em〉 strain ATCC 17453. We have tested camphor, borneol, oxidized camphor metabolites and known bacterial attractants (〈span〉d〈/span〉)-glucose, (〈span〉d〈/span〉) - and (〈span〉l〈/span〉)-glutamic acid for their elicitation chemotactic behavior. In addition, we have used 1-phenylimidazole, a P450〈sub〉cam〈/sub〉 inhibitor, to investigate if P450〈sub〉cam〈/sub〉 plays a role in the chemotactic ability of 〈em〉P. putida〈/em〉 in the presence of camphor. We found that camphor, a chemoattractant, became toxic and chemorepellent when P450〈sub〉cam〈/sub〉 was inhibited. We have also evaluated the effect of borneol on chemotaxis and found that the bacteria chemotaxed away from camphor in the presence of borneol. This is the first report of the chemotactic behaviour of 〈em〉P. putida〈/em〉 ATCC 17453 and the essential role of P450〈sub〉cam〈/sub〉 in this process.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Guang-hua Wang, Jing-jing Wang, Bin Yue, Xue Du, He-he Du, Min Zhang, Yong-hua Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉High-mobility group box 2 (HMGB2) is a non-histone chromosomal protein that involved diverse functions such as transcriptional regulation and innate immune responses in mammalian. In teleost, very limited studies on HMGB2 proteins have been documented. Black rockfish (〈em〉Sebastes schlegelii〈/em〉) is an economic fish species and cultured worldwide. However, the study of black rockfish about immunology is very scarce. In the present study, a HMGB2 homologue gene (〈em〉SsHMGB2〈/em〉) was identified and characterized in black rockfish. The open reading frame of 〈em〉SsHMGB2〈/em〉 is 648 bp, and the deduced amino acid sequence of 〈em〉SsHMGB2〈/em〉 shares 74.4%–91.2% overall sequence identities with the HMGB2 proteins of several fish species. In silico analysis identified several conserved features, including two basic HMG boxes and an acidic C-terminal tail composed of 24 Asp/Glu residues. Expression of 〈em〉SsHMGB2〈/em〉 occurred in multiple tissues and was upregulated during pathogens infection. Recombinant SsHMGB2 (rSsHMGB2) exhibited apparent binding activities against DNA. 〈em〉In vivo〈/em〉 studies showed that the expressions of multiple immune-related genes in head kidney were significantly enhanced when black rockfish were treated with rSsHMGB2. Furthermore, rSsHMGB2 reduced pathogen dissemination and replication in fish kidney and spleen. Taken together, these results suggest that SsHMGB2 possesses apparent immunoregulatory properties and played a role in fighting bacterial infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Sai-Wei Chen, Chun-Hung Liu, Shao-Yang Hu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Bacteria-induced diseases are a major cause of mortality in aquaculture. Probiotics have commonly been used to replace antibiotics for prophylactic biocontrol in aquaculture. In the present study, 〈em〉Paenibacillus ehimensis〈/em〉 NPUST1 was isolated from a tilapia culture pond. This probiotic has bacteriocin-like activities against 〈em〉Aeromonas hydrophila〈/em〉 and was characterized by biochemical analysis and 16S rDNA sequencing. The physiochemical properties of a crude extract of the bacteriocin-like substance revealed low pH and high thermal tolerance. The substance exhibited broad-spectrum antimicrobial activity against diverse aquatic pathogens, food spoilage, clinical pathogens, and plant pathogens. The effect of dietary supplementation with 〈em〉P. ehimensis〈/em〉 NPUST1 was evaluated in regard to the growth of Nile tilapia (〈em〉Oreochromis niloticus〈/em〉) and immunity against pathogenic infection. The results showed significantly increased weight gain (WG), feed conversion ratio (FCR), and feed efficiency (FE) in Nile tilapia fed 〈em〉P. ehimensis〈/em〉 NPUST1 for 2 months compared with fish fed a control diet. When challenged with 〈em〉A. hydrophila〈/em〉 and 〈em〉S. iniae,〈/em〉 the fish fed 〈em〉P. ehimensis〈/em〉 NPUST1 also exhibited a higher survival rate than fish fed the control diet. The immune parameters revealed that the 〈em〉P. ehimensis〈/em〉 NPUST1-fed fish had significantly higher phagocytic activity, respiratory burst, and superoxide dismutase (SOD) of the head kidney leukocytes, as well as higher serum lysozyme activity and expression of cytokines TNF-α and IL-1β than the fish fed the control diet. These results indicate that dietary supplementation with 〈em〉P. ehimensis〈/em〉 NPUST1 improved the growth performance, immunity, and disease resistance in Nile tilapia.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Cheng-cai Zheng, Xin-yi Cai, Meng-meng Huang, Idefonce Mkingule, Cong Sun, Shi-Chao Qian, Zhen-ju Wu, Bing-nan Han, Hui Fei〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Japanese eel (〈em〉Anguilla japonica〈/em〉) has become a commercially important fish species all over the world. High-density aquaculture has led to congestion and contributed to bacterial infection outbreaks that have caused high mortality. Therefore a 56-days feeding trial was conducted to determine the effects of dietary 〈em〉Bacillus amyloliquefaciens〈/em〉 (GB-9) and 〈em〉Yarrowia lipolytica〈/em〉 lipase2 (YLL2) on growth performance, digestive enzymes activity, innate immunity and resistance to pathogens of 〈em〉A. japonica〈/em〉. Fish growth performance was significantly affected by dietary YLL2 supplementation but not by GB-9. Fish fed diets with YLL2 at 2.0 g/kg diet in combination of high and low levels of GB-9 (5.0 g/kg and 2.0 g/kg) produced the highest growth. For digestive enzyme, lipase and trypsin activities was promoted by dietary containing YLL2, while amylase activities was increased by dietary containing YLL2, GB-9 single or combination. For innate immunity, the mucus lysozyme activity, leukocytes phagocytosis activity and reactive oxygen species level of skin, peroxidase and lysozyme activity of serum were enhanced in fish fed with GB-9 compared to those in control group (p 〈 0.05). The highest resistance to 〈em〉Vibrio anguillarum〈/em〉 and 〈em〉Aeromonas hydrophila〈/em〉 was determined in fish fed with 5.0 g kg〈sup〉−1〈/sup〉 GB-9 + 2.0 g/kg YLL2. This study demonstrated that GB-9 and YLL2 enhanced non-specific immune defense system of 〈em〉A. japonica〈/em〉, providing them with higher resistance to pathogens. The present results suggested that the combination of these supplements could be considered as potential biological additives for aquaculture farmed fish.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Xianyong Bu, Xuqiu Lian, Yi Wang, Chengzeng Luo, Shengqiang Tao, Yilu Liao, Jiaming Yang, Aijing Chen, Yuhong Yang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The aim of the present study was to investigate effects of dietary yeast culture on immune response related to TLR2-MyD88-NF-kβ signaling pathway, antioxidant capability and disease resistance against 〈em〉Aeromonas hydrophila〈/em〉 for Ussuri catfish (〈em〉Pseudobagrus ussuriensis〈/em〉). A total of 240 Ussuri catfish (mean weight of 7.39 ± 0.32 g) were randomly distributed into four groups that fed diets containing 0 (Y0), 10 (Y1), 20 (Y2) and 30 (Y3) g kg〈sup〉−1〈/sup〉 yeast culture for 8 weeks. The results indicated that dietary 10 g kg〈sup〉−1〈/sup〉 yeast culture supplementation significantly down-regulated mRNA levels of TLR2, MyD88, NF-kβ p65, IL-1β and IL-8 in the liver tissue compared with the control group (〈em〉P〈/em〉 〈 0.05). Simultaneously, serum lysozyme (LZM) activity, respiratory burst activity (RBA) of phagocytes, plasma alkaline phosphatase (AKP) activity and immunoglobulin M (IgM) content were significantly improved in fish fed Y1 diet (〈em〉P〈/em〉 〈 0.05). Fish fed Y1 diet had significantly higher serum alternative complement pathway activity (ACH50) and plasma complement 3 (C3) content than the Y3 group (〈em〉P〈/em〉 〈 0.05). However, no significant differences were observed in plasma acid phosphatase (ACP) activity and complement 4 (C4) content among the groups (〈em〉P〈/em〉 〉 0.05). Fish cumulative mortality rate (CMR) in the Y1 and Y2 groups were significantly lower than that in Y0 and Y3 groups (〈em〉P〈/em〉 〈 0.05), and the lowest CMR was observed in the Y1 group after challenge by 〈em〉A. hydrophila〈/em〉. The highest hepatic superoxide dismutase and glutathione peroxidase activities, total antioxidant capacity and the lowest malondialdehyde content were found in Y1 group, but no significant difference was found in hepatic catalase activity among the groups (〈em〉P〈/em〉 〉 0.05). These results demonstrate that dietary 10 g kg〈sup〉−1〈/sup〉 yeast culture could effectively improve the immunity, antioxidant capability and disease resistance against 〈em〉A. hydrophila〈/em〉 for Ussuri catfish and could down-regulate the mRNA expression levels of pro-inflammatory cytokines modulated by TLR2-MyD88-NF-kβ signaling pathway.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Tao Wang, Xin Wen, Yadong Hu, Xinyu Zhang, Dan Wang, Shaowu Yin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Copper nanoparticles (Cu NPs) are a new pollutant in aquaculture, representing a hazard to aquatic organisms. We investigated the effects of Cu NPs exposure on oxidative stress, apoptosis and immune response in an economically important model species, 〈em〉Takifugu fasciatus〈/em〉. The juvenile fish were exposed to control, 20 or 100 μg Cu NPs/L for 30 days. The growth of 〈em〉T. fasciatus〈/em〉 was inhibited after Cu NPs exposure. Copper accumulation in liver increased with increasing Cu NPs dose. Oxidative stress indicators [malondialdehyde (MDA), total superoxide dismutase (T-SOD), catalase (CAT) and glutathione (GSH)], apoptosis index and activities of caspases (caspase-3, caspase-9) were all increased with the increase of Cu NPs concentration in liver. With an increase in Cu NPs dose, the activities of succinate dehydrogenase (SDH) and Na〈sup〉+〈/sup〉-K〈sup〉+〈/sup〉-ATPase as well as cytochrome c (Cyt-c) concentration in mitochondria decreased, accompanied by increased Cyt-c concentration in cytosol. Apoptosis-related gene expressions of 〈em〉p53〈/em〉, 〈em〉caspase-3〈/em〉, 〈em〉caspase-9〈/em〉 and 〈em〉Bax〈/em〉 were increased with the increase of Cu NPs dose. However, the opposite result was found in 〈em〉Bcl2〈/em〉 expression. The physiological indicators of immune response [heat shock protein 70 (HSP70), heat shock protein 90 (HSP90), immunoglobulin M (IgM) and lysozyme (LZM)] as well as the mRNA levels of 〈em〉HSP70〈/em〉, 〈em〉HSP90〈/em〉, 〈em〉IgM〈/em〉 and 〈em〉C-LZM〈/em〉 were all increased after Cu NPs exposure〈em〉.〈/em〉 Our results will be helpful in understanding the mechanism of Cu NPs toxicity in 〈em〉T. fasciatus〈/em〉.〈/p〉〈/div〉 〈/div〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1050464818306867-fx1.jpg" width="278" alt="Image 1" title="Image 1"〉〈/figure〉〈/p〉〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Junguo Ma, Xi Chen, Guangyuan Xin, Xiaoyu Li〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The present study aimed to determine the chronic toxicity of 1-methyl-3-octylimidazolium bromide ([C〈sub〉8〈/sub〉mim]Br) on the silver carp to further reveal the toxicological mechanisms of ionic liquids. Chronic exposure of silver carp to [C〈sub〉8〈/sub〉mim]Br at concentrations of 1.095 and 4.380 mg/L for 60 d was conducted under laboratory conditions. The results revealed that chronic exposure to [C〈sub〉8〈/sub〉mim]Br inhibited the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and reduced glutathione (GSH) levels while markedly increasing malondialdehyde (MDA) and protein carbonyl (PC) levels in fish spleen, indicating that [C〈sub〉8〈/sub〉mim]Br treatment induced oxidative stress. Additionally, long-term exposure to [C〈sub〉8〈/sub〉mim]Br markedly upregulated the expressions of nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), IL-6, tumour necrosis factor-α (TNF-α), and interferon-γ (IFN-γ); altered the levels of transforming growth factor-β (TGF-β); and increased the mRNA levels of p38MAPK, c-fos, c-jun, and c-myc, suggesting that long-term exposure to [C〈sub〉8〈/sub〉mim]Br might promote the inflammatory response in fish spleen and that p38MAPK/NF-κB signalling may potentially be involved in this process. Moreover, [C〈sub〉8〈/sub〉mim]Br-exposure altered lysozyme activity and complement 3 (C3) and immunoglobulin M (IgM) content, indicating that chronic [C〈sub〉8〈/sub〉mim]Br exposure also has immunotoxic effects on silver carp. Furthermore, we also found that [C〈sub〉8〈/sub〉mim]Br exposure reduced miR-125b levels, altered miR-143 levels, and upregulated miR-155 and miR-21 levels, suggesting that these miRNAs may be involved in the [C〈sub〉8〈/sub〉mim]Br-induced inflammatory response in fish spleen. In summary, the present study indicates that chronic exposure to [C〈sub〉8〈/sub〉mim]Br induces inflammation in fish spleen and that oxidative stress-mediated p38MAPK/NF-κB signalling and miRNAs may play a key role in this process.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Chaozheng Li, Shaoping Weng, Jianguo He〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉As invertebrates, shrimps rely on multiple innate defense reactions, including humoral immunity and cellular immunity to recognize and eliminate various invaders, such as viruses. White spot syndrome virus (WSSV) causes the most prevalent and devastating viral disease in penaeid shrimps, which are the most widely cultured species in the coastal waters worldwide. In the last couple of decades, studies about WSSV implicate a dual role of the immune system in protecting shrimps against the infection; these studies also explore on the pathogenesis of WSSV infection. Herein, we review our current knowledge of the innate immune responses of shrimps to WSSV, as well as the molecular mechanisms used by this virus to evade host immune responses or actively subvert them for its own benefit. Deciphering the interactions between WSSV and the shrimp host is paramount to understanding the mechanisms that regulate the balance between immune-mediated protection and pathogenesis during viral infection and to the development of a safe and effective WSSV defensive strategy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Xin Zhang, Jialong Shi, Yulong Sun, Yusuf Jibril Habib, Huiping Yang, Ziping Zhang, Yilei Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In recent years, the abalone aquaculture industry has been threatened by the deteriorating environmental conditions, such as hypoxia and thermal stress in the hot summers. It is necessary to investigate the molecular mechanism in response to these environmental challenges, and subsequently understand the immune defense system. In this study, the transcriptome profiles by RNA-seq of hemocytes from the small abalone 〈em〉Haliotis diversicolor〈/em〉 after exposure to hypoxia, thermal stress, and hypoxia plus thermal stress were established. A total of 103,703,074 clean reads were obtained and 99,774 unigenes were assembled. Of the 99,774 unigenes, 47,154 and 20,455 had homologous sequences in the Nr and Swiss-Prot protein databases, while 16,944 and 10,840 unigenes could be classified by COG or KEGG databases, respectively. RNAseq analysis revealed that the differentially expressed genes (DEGs) after challenges of hypoxia, thermal stress, or hypoxia plus thermal stress were 24,189, 29,165 and 23,665, among which more than 3000 genes involved in at least 230 pathways, including several classical immune-related pathways. The genes and pathways that were involved in immune response to hypoxia/thermal challenges were identified by transcriptome analysis and further validated by quantitative real-time PCR and RNAi technology. The findings in this study can provide information on 〈em〉H. diversicolor〈/em〉 innate immunity to improve the abalone aquaculture industry, and the analysis of the potential immune-related genes in innate immunity signaling pathways and the obtained transcriptome data can provide an invaluable genetic resource for the study of the genome and functional genes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Thanthrige Thiunuwan Priyathilaka, S.D.N.K. Bathige, Seongdo Lee, Bo-Hye Nam, Jehee Lee〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Toll-like receptors (TLRs) are well-known pattern recognition receptors that play key immunological roles in a diverse range of organisms. In this study, two novel invertebrate TLRs from disk abalone (designated as AbTLR-A and AbTLR-B) were identified and functionally characterized for the first time. AbTLR-A and AbTLR-B comprised the typical TLR domain architecture containing an extracellular leucine-rich repeat domain, transmembrane domain, and Toll/interleukin-1 receptor domain. Expressional analysis revealed that both TLRs were constitutively expressed at all the early embryonic stages of disk abalone analyzed, with the highest level of 〈em〉AbTLR-A〈/em〉 found at the 16-cell stage and 〈em〉AbTLR-B〈/em〉 at the trochophore stage. According to tissue distribution analysis, prominent mRNA expression of 〈em〉AbTLR-A〈/em〉 and 〈em〉AbTLR-B〈/em〉 was detected in the hemocytes and gills, respectively. 〈em〉AbTLR-A〈/em〉 and 〈em〉AbTLR-B〈/em〉 mRNAs were significantly up-regulated in response to Gram-negative 〈em〉Vibrio parahemolyticus〈/em〉, Gram-positive 〈em〉Listeria monocytogenes〈/em〉, and viral hemorrhagic septicemia virus injections in abalone hemocytes and gills. Overexpression of AbTLR-A and AbTLR-B in HEK293T cells directly activated nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) responsive reporters. Neither TLRs showed a high response to pathogen-associated molecular patterns 〈em〉in vitro〈/em〉. Co-expression of AbTLR-A and AbTLR-B with AbMyD88-2 and AbMyD88-X activated NF-κB-responsive reporters in a synergetic manner. These findings demonstrate the involvement of AbTLR-A and AbTLR-B in abalone innate immunity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Mona Saleh, Gokhlesh Kumar, Abdel-Azeem S. Abdel-Baki, Mohamed A. Dkhil, Mansour El-Matbouli, Saleh Al-Quraishy〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Ichthyophthirius multifiliis〈/em〉, a ciliated protozoan parasite, causes ichthyophthiriasis and leads to considerable economic losses to the aquaculture industry. Understanding the fish immune response and host-parasite interactions could support developing novel strategies for better disease management and control. Fish skin mucus is the first line of defence against infections through the epidermis. Yet, the common carp, 〈em〉Cyprinus carpio〈/em〉, protein-based defence strategies against infection with 〈em〉I. multifiliis〈/em〉 at this barrier remain elusive. The skin mucus proteome of common carp was investigated at 1 day and 9 days post-exposure with 〈em〉I. multifiliis〈/em〉. Using nano-LC ESI MS/MS and statistical analysis, the abundance of 19 immune related and signal transduction proteins was found to be differentially regulated in skin mucus of common carp in response to 〈em〉I. multifiliis〈/em〉. The analysis revealed increased abundance values of epithelial chloride channel protein, galactose-specific lectin nattection, high choriolytic enzyme 1 (nephrosin), lysozyme C, granulin and protein-glutamine gamma-glutamyltransferase 2 in 〈em〉I. multifiliis-〈/em〉exposed carp skin mucus. Multiple lectins and a diverse array of distinct serpins with protease inhibitor activity were identified likely implicated in lectin pathway activation and regulation of proteolysis, indicating that these proteins contribute to the carp innate immune system and the protective properties of skin mucus. The results obtained from this proteomic analysis enables a better understanding of fish host response to parasitic infection and gives insights into the key role skin mucus plays in protecting fish against deleterious effects of 〈em〉I. multifiliis〈/em〉.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Fufa Qu, Jianzhou Tang, Jinting Liao, Bei Chen, Peng Song, Wenjie Luo, Ding Xiong, Tianting Liu, Qianting Gao, Shuangqing Lu, Zhen Liu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Mitogen-activated protein kinase kinase 6 (MKK6) is an essential component of the p38MAPK signaling pathway, which is involved in the modulation of inflammation, cell apoptosis and survival responses in mammals. However, the function of MKK6s in teleosts is still unclear. In this study, a fish MKK6 homolog (〈em〉Ci〈/em〉MKK6) was first identified from the grass carp (〈em〉Ctenopharyngodon idella〈/em〉), a freshwater fish. 〈em〉Ci〈/em〉MKK6 cDNA encodes a putative protein of 357 amino acids that contains conserved structural characteristics of the MKK6 family, including the S_TKc domain, SVAKT motif and DVD site. The deduced 〈em〉Ci〈/em〉MKK6 protein exhibits high sequence homology with other reported fish MKK6s and shares the closest relationship with MKK6 from 〈em〉Danio rerio〈/em〉. Quantitative real-time PCR (qRT-PCR) analysis revealed that 〈em〉Ci〈/em〉MKK6 mRNA was widely expressed in all tested tissues and stages of embryonic development. Additionally, the transcript levels of 〈em〉Ci〈/em〉MKK6 in the intestine were significantly upregulated in response to bacterial muramyl dipeptide (MDP) and L-Ala-γ-D-Glu-meso-diaminopimelic acid (Tri-DAP) stimulation. Moreover, subcellular localization analysis indicated that 〈em〉Ci〈/em〉MKK6 was distributed in both the cytoplasm and the nucleus of HEK293T cells. Finally, overexpression of 〈em〉Ci〈/em〉MKK6 significantly enhanced the transcriptional activity of the AP-1 reporter gene in HEK293T cells. Overall, these findings may help better clarify the immune function of teleost MKK6s and provide new insight into the immune defense mechanisms of grass carp.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Liting Wu, Shengli Fu, Xiaoxue Yin, Wenna Leng, Zheng Guo, Anli Wang, Jianmin Ye〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Affinity maturation of the antibody response, a process of antibody affinity increasing over response, is one of the key features of the mammalian immune system. However, the process is incompletely understood in teleost, including channel catfish (〈em〉Ictalurus punctaus〈/em〉). In this study, IgM affinity maturation in channel catfish was investigated by estimating the kinetics of antibody affinity using ELISA and ELISPOT assays. Fish were immunized with a T-cell dependent antigen (TNP-KLH), and individual serum IgM antibody titers and affinities, and IgM〈sup〉+〈/sup〉 antibody-secreting cells (ASCs) in peripheral blood were analyzed over a period of 14 weeks. A detectable serum anti-TNP response developed by 2-weeks post-immunization, and the maximal antibody production was observed by 6-weeks post-immunization. The average affinity of anti-TNP serum antibody increased consistently and reached the maximum by 10-weeks post-immunization. The increase of antibody affinity beyond the point of optimal antibody titer revealed that the affinity maturation of IgM antibody response occurred in channel catfish. Dissection of dynamics of individual affinity subpopulations indicated that a significant proportion of low affinity subpopulations appeared at early response, and high affinity subpopulations appeared predominantly at later, resulting in a 100-fold increase in affinity over response. Additional, TNP〈sup〉+〈/sup〉 IgM〈sup〉+〈/sup〉 ASCs was detected by 2-weeks post-immunization and achieved the maximal number by 6-weeks post-immunization. Using an inhibition ELISPOT assay, the findings of a consistent increase in the average affinity of secreted IgM antibody by peripheral blood ASCs, as the immune response progressed, confirmed the occurrence of the affinity maturation. Taken together, the results of this study indicated that affinity maturation occurred in channel catfish following immunization with a TD antigen TNP-KLH.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Fish & Shellfish Immunology, Volume 84〈/p〉 〈p〉Author(s): Weihua Gao, Shuai Li, Qiaoqing Xu, Dashi Zhu, Qin Zhang, Kai Luo, Wenbing Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The CXC chemokine receptors (CXCRs) play critical roles in innate and adaptive immune systems. In this study, six Asian swamp eel (〈em〉Monopterus albus〈/em〉) CXCRs (〈em〉Ma〈/em〉CXCR1–4) were identified and their molecular characterization and expression patterns were analyzed. The open reading frames (ORFs) of 〈em〉Ma〈/em〉CXCR1a, 〈em〉Ma〈/em〉CXCR1b, 〈em〉Ma〈/em〉CXCR2, 〈em〉Ma〈/em〉CXCR3a, 〈em〉Ma〈/em〉CXCR3b, and 〈em〉Ma〈/em〉CXCR4 were 1074 bp (base pairs), 1080 bp, 1125 bp, 1146 bp, 1083 bp, and 1140 bp, and encoded proteins of 357 aa (amino acids), 359 aa, 374 aa, 381 aa, 360 aa, and 379 aa, respectively. All these CXCRs have seven conserved transmembrane domains and four cysteines (with the exception of 〈em〉Ma〈/em〉CXCR3b). Multiple sequence alignment revealed that the 〈em〉Ma〈/em〉CXCRs possess a typical G-protein receptor family 1 signature and a DRY motif. There are also one to four potential N-glycosylation sites in the extracellular regions of the 〈em〉Ma〈/em〉CXCRs, mainly distributed in the N-terminus and extracellular hydrophilic loop (ECL) 2 region. Phylogenetic analysis demonstrated that the 〈em〉Ma〈/em〉CXCRs were clustered together with homologous proteins from other fish. Taken together with the amino acid identity and similarity analysis, these results suggested that the 〈em〉Ma〈/em〉CXCRs are conserved with other homologous genes, in which CXCR4 is more conserved than CXCR1–3. The 〈em〉Ma〈/em〉CXCRs loci showed conserved synteny among teleost fish, and we found that human CXCR1 shares a common ancestor with fish CXCR1a. 〈em〉Ma〈/em〉CXCRs were constitutively expressed in a wide range of tissues (especially in immune-related tissues) with different expression levels, suggesting that the 〈em〉Ma〈/em〉CXCRs have different roles in un-stimulated tissues, and may play vital roles under normal conditions. 〈em〉Ma〈/em〉CXCRs showed different fold changes in the spleen after 〈em〉Aeromonas veronii〈/em〉 and polyinosinic-polycytidylic acid (poly I:C) challenge, which suggested that 〈em〉Ma〈/em〉CXCR1a and 〈em〉Ma〈/em〉CXCR3a have longer antiviral activities compared with their antibacterial functions, and that 〈em〉Ma〈/em〉CXCR1b possesses stronger antiviral than antibacterial activity. 〈em〉Ma〈/em〉CXCR4 may play vital roles during bacterial and viral infection; however, 〈em〉Ma〈/em〉CXCR2 has relatively small effect in antibacterial and antiviral responses. The differential responses of these genes to bacteria and poly I:C implied the differences in the mechanisms of defense against viruses and bacteria.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Yuji Takeda, Tomoyuki Kato, Nobuhito Nemoto, Akemi Araki, Mohammad Yeashin Gazi, Hidetoshi Nara, Hironobu Asao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Inflammation can occur via different mechanisms, such as via acute and chronic responses, on numerous occasions and function accordingly through various roles. There are more than five subsets of neutrophils; neutrophilic heterogeneity is modulated by the inflammatory condition. To understand the characteristics of inflammation, identification of atypical neutrophils is important. In this study, we found that the expression of eotaxin receptor (CD193) on atypical neutrophils in the duodenum is augmented in IL-21 isoform transgenic (Tg) mice. In a series of studies, we have established a Tg mouse strain to further investigate the functions of IL-21 〈em〉in vivo〈/em〉. Interestingly, Tg mice immunized with ovalbumin (OVA) were more sensitive to OVA-induced systemic anaphylaxis as compared with wild type mice with duodenal and splenic gross congestion. Further analysis conducted in the duodenum of Tg mice revealed that only the number of neutrophils migrating into the duodenum was significantly increased prior to immunization. Previous studies have shown that the gastrointestinal compartment and the spleen constantly produce eotaxin, which regulates basal levels of tissue eosinophils. Therefore, we analyzed CD193 expression on neutrophils and eosinophils. As expected, its expression by duodenal neutrophils was upregulated in Tg mice. Furthermore, the addition of IL-21 into bone marrow cell culture increased the number of CD193〈sup〉+〈/sup〉 neutrophils, which easily migrated into the duodenum. These observations suggested that CD193〈sup〉+〈/sup〉 neutrophils increase in number under inflammatory conditions due to chronic IL-21 production.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1043466618301972-fx1.jpg" width="449" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Mohamed S. Zaibi, Małgorzata A. Kępczyńska, Parvathy Harikumar, Suliman Y. Alomar, Paul Trayhurn〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Expression of GPCR fatty acid sensor/receptor genes in adipocytes is modulated by inflammatory mediators, particularly IL-1β. In this study we examined whether the IL-1 gene superfamily member, IL-33, also regulates expression of the fatty acid receptor genes in adipocytes. Human fat cells, differentiated from preadipocytes, were incubated with IL-33 at three different dose levels for 3 or 24 h and mRNA measured by qPCR. Treatment with IL-33 induced a dose-dependent increase in GPR84 mRNA at 3 h, the level with the highest dose being 13.7-fold greater than in controls. Stimulation of 〈em〉GPR84〈/em〉 expression was transitory; the mRNA level was not elevated at 24 h. In contrast to 〈em〉GPR84〈/em〉, IL-33 had no effect on 〈em〉GPR120〈/em〉 expression. IL-33 markedly stimulated expression of the 〈em〉IL1B〈/em〉, 〈em〉CCL2〈/em〉, 〈em〉IL6〈/em〉, 〈em〉CXCL2〈/em〉 and 〈em〉CSF3〈/em〉 genes, but there was no effect on 〈em〉ADIPOQ〈/em〉 expression. The largest effect was on 〈em〉CSF3〈/em〉, the mRNA level of which increased 183-fold over controls at 3 h with the highest dose of IL-33; there was a parallel increase in the secretion of G-CSF protein into the medium. It is concluded that in human adipocytes IL-33, which is synthesised in adipose tissue, has a strong stimulatory effect on the expression of cytokine and chemokine genes, particularly 〈em〉CSF3〈/em〉, and on the expression of GPR84, a pro-inflammatory fatty acid receptor.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Juey-Ming Shih, Yao-Ming Shih, Yu-Chen Hou, Man-Hui Pai, Chiu-Li Yeh, Sung-Ling Yeh〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study investigated the effects of a fish oil-based lipid emulsion (FO) on local skeletal muscle and remote renal damage at 72 h post-reperfusion in a murine model of hind limb ischemia-reperfusion (IR) injury. Mice were assigned to 1 sham group and 3 IR groups. The IR groups were treated daily with either saline or FO from 3 days prior to limb ischemia till 3 days after reperfusion. Limb IR was induced by applying a 4.5-oz orthodontic rubber band above the left greater trochanter for 120 min followed by band-released reperfusion for 72 h. Mice were then sacrificed to harvest blood, muscle, and kidney for analysis. The results showed that IR injury led to upregulation of pro-inflammatory monocytes in blood, infiltration of leukocytes into injured muscle, and over-expression of pro-inflammatory genes in muscle and kidney tissues. Supplementing FO either before or after IR injury alleviated IR-induced inflammatory gene expressions in muscle and kidney tissues. Furthermore, FO given after IR injury reduced circulating pro-inflammatory monocytes, limited muscle leukocytic infiltration, and improved renal histology. These results suggest that FO may protect the muscles from IR injury. FO given after IR injury can better downregulate the inflammation seen in IR-induced remote kidney injury.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Yohei Kanamori, Masaru Murakami, Tohru Matsui, Masayuki Funaba〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hepcidin, a liver-derived hormone, negatively regulates circulating iron levels through an increase in its expression in response to iron overload. Inflammation also increases production of hepcidin, potentially leading to inflammatory anemia. We previously revealed that proinflammatory cytokine interleukin (IL)-1β increased hepcidin expression through its transcriptional stimulation in hepatocytes. Induction of CCAAT-enhancer-binding protein (C/EBP) δ and IL-6 in response to IL-1β treatment stimulated hepcidin transcription via the C/EBP-binding site (C/EBP-BS) and signal transducer and activator of transcription (STAT)-BS on the hepcidin promoter, respectively. Here, we show an additional pathway responsible for IL-1β-induced hepcidin transcription. IL-1β stimulated phosphorylation of c-Jun N-terminal kinase (JNK) and its substrates c-Jun and JunB. SP600125, a JNK inhibitor, blocked IL-1β-induced phosphorylation of c-Jun and JunB as well as IL-1β-induced expression and transcription of hepcidin. Reporter assays for hepcidin transcription revealed that reporters with mutations of cAMP response element (CRE) site B, a putative Jun binding element, decreased responsiveness to IL-1β, and that activated JunB, but not c-Jun, conferred IL-1β-induced hepcidin transcription. Furthermore, binding of JunB to hepcidin promoter was increased by IL-1β. The present study indicated that IL-1β activates JNK and subsequently stimulates JunB activation, leading to hepcidin transcription via CRE site B on the hepcidin promoter. The present experiment provides novel insights into the molecular mechanisms underlying induction of hepcidin by inflammation and alteration of iron homeostasis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Rezvan Noroozi, Mir Davood Omrani, Seyed Abdulmajid Ayatollahi, Arezou Sayad, Athar Ata, Hamid Fallah, Mohammad Taheri, Soudeh Ghafouri-Fard〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Previous studies have highlighted the role of immune dysregulation in suicide behavior. Interleukin (IL)-8 is a chemokine with neuroprotective effects whose lower serum concentrations have been detected in individuals committed suicide. In the present study, we genotyped three single nucleotide polymorphisms (SNPs) within 〈em〉IL-8〈/em〉 gene (rs4073, rs2227306 and rs1126647) in 229 individuals who attempted suicide with soft suicide methods, 235 suicide victims and 290 individuals without any history of psychiatric disorders or suicide attempt. The T allele of rs4073 was significantly over-represented in suicide attempt group compared with both control and completed suicide groups (adjusted P values of 8.3E-7 and 9.8E-8 respectively). This SNP was associated with suicide attempt in both dominant and co-dominant models (P values of 6.2E−9 and 4.3 E−8 respectively). The genotype and allele frequencies of other SNPs were not significantly different among the three study groups. The T C A haplotype (rs4073, rs2227306 and rs1126647 respectively) were significantly less prevalent in completed suicide group compared with suicide attempt group (OR (95% CI) = 0.63 (0.46–0.86), adjusted P value = 0.03). Besides, the A T A haplotype has significant lower frequency in individuals who attempted soft suicide compared with controls (OR (95% CI) = 0.44 (0.26–0.75), adjusted P value = 0.02). However, this haplotype was significantly more prevalent in individuals attempted hard methods compared with those attempted soft methods (OR (95% CI) = 2.21 (1.26–3.87), adjusted P value = 0.04). The present study provided further evidence for the role of IL-8 in suicide behavior.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Chao-Ping Wang, Teng-Hung Yu, Cheng-Ching Wu, Wei-Chin Hung, Chia-Chang Hsu, I-Ting Tsai, Wei-Hua Tang, Fu-Mei Chung, Jer-Yiing Houng, Yau-Jiunn Lee, Yung-Chuan Lu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Secreted frizzled-related protein-5 (Sfrp5) known as secreted antagonist binds to Wnt protein. It has been shown to be downregulated by histone acetylation and promoter methylation, and to function as a tumor suppressor gene by inducing apoptosis in renal cell cancer cells. However, its relationship with chronic kidney disease (CKD) has not been well studied. Our objective was to investigate the effect of plasma Sfrp5 levels in subjects with and without CKD. Plasma Sfrp5 levels were determined by enzyme-linked immunosorbent assays in 196 consecutive patients with acute ST-segment elevation myocardial infarction (STEMI). CKD was defined as an estimated glomerular filtration rate (eGFR) 〈60 ml/min per 1.73 m〈sup〉2〈/sup〉. For the purpose of this study, stage 1 or 2 CKD patients (eGFR ≥ 60 ml/min per 1.73 m〈sup〉2〈/sup〉) were classified as not having CKD. With increasing Sfrp5 tertiles, the patients had higher frequencies of hypertension, stage 4 or 5 CKD, and waist-to-hip ratio, incrementally lower eGFRs and serum hemoglobin levels, and higher levels of blood urine nitrogen (BUN), creatinine, and adiponectin. Multivariate logistic regression analysis showed that an increased plasma Sfrp5 level was independently associated with CKD for all subjects (adjusted odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02–1.14; p = 0.011). Sfrp5 was also significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin. When the patients were stratified by age, plasma Sfrp5 level was independently related to CKD for patients 〉65 years old (adjusted OR, 1.10; 95% CI, 1.00–1.20; p = 0.045), however, the association was not significant for those 〈65 years old. In addition, Sfrp5 was significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin in patients 〉65 years old. Our results suggest that Sfrp5 may play a role in the pathogenesis of CKD in acute STEMI patients who are older than 65 years.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Betsy Annel González-Quezada, Hilario Flores-Aguilar, Alberto Olaya-Vargas, Haydee Salazar-Rosales, Martín Pérez-García, Luis Manuel Valero-Saldaña, Brenda Lizeth Acosta-Maldonado, Roberto Ovilla-Martínez, Clara Gorodezky〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Acute lymphoblastic leukemia (ALL), the most common type of cancer in children worldwide, has one of the highest incidence rates in Mexico. It is a multifactorial disease and different cytokine single nucleotide polymorphisms (SNP), have been associated with ALL expression. Few studies have been published analyzing 〈em〉IFNG〈/em〉 +874 T/A and 〈em〉IL2〈/em〉 −330 G/T in this type of leukemia. These SNPs are involved in high or low expression, and are central to cellular immunity, influencing greatly tumor growth. The purpose of this work was to explore the association of 〈em〉IFNG〈/em〉 +874 A/T (rs2430561) and 〈em〉IL2〈/em〉 −330 G/T (rs2069762) SNPs with ALL susceptibility and/or protection in 488 Mexican Mestizos patients, as compared to 950 Mexican Mestizo healthy controls. The results demonstrated that 〈em〉IFNG〈/em〉 +874 T allele (pc = 0.00004, OR = 0.673) and the TT genotype (pc = 0.00015, OR = 0.349), protect against ALL expression with no specific gender association; however, the TT homozygote genotype (vs. TA+AA) seems more protective in males (pc = 0.00683). 〈em〉IL2〈/em〉 −330 G/T does not contribute to the development of ALL. In healthy Mexicans, the most common genotypes for 〈em〉IL2〈/em〉 and 〈em〉IFNG〈/em〉, are the low cytokine producers, suggesting that the genetic background in this ethnic group, may be partly responsible for the high incidence of ALL. These results show for the first time in Mexicans, the relevant role that 〈em〉IFNG〈/em〉 SNP has in the genetic etiology of ALL. Thus, a large group of patients belonging to different ethnicities will be very helpful to study in order to demonstrate if these SNPs contribute to the genetic etiology of ALL, as shown here in Mexican Mestizos.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Jorge Rodrigues de Sousa, Raimunda do Socorro da Silva Azevedo, Arnaldo Jorge Martins Filho, Marialva Tereza Ferreira de Araujo, Ermelinda do Rosário Moutinho Cruz, Barbara Cristina Baldez Vasconcelos, Ana Cecilia Ribeiro Cruz, Consuelo Silva de Oliveira, Livia Caricio Martins, Beatriz Helena Baldez Vasconcelos, Livia Medeiros Neves Casseb, Jannifer Oliveira Chiang, Juarez Antonio Simões Quaresma, Pedro Fernando da Costa Vasconcelos〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Zika virus (ZIKV) has caused substantial concern worldwide owing to its association with severe birth defects, such as microcephaly and other congenital malformations. Inflammasomes, i.e., multi-protein complexes that induce inflammation and pyroptosis, are predicted to contribute to the immune response to this flavivirus. Accordingly, in this study, the 〈em〉in situ〈/em〉 inflammasome response was evaluated in fatal cases of ZIKV-linked microcephaly. Brain tissue samples were collected from eight babies, including four ZIKV-positive microcephalic neonates who died after birth and four flavivirus-negative neonatal controls who died of other causes and whose central nervous system (CNS) architecture was preserved. In the ZIKV-positive newborn/stillbirth babies, the major histopathological alterations included atrophy of the cortical layer, a predominance of mononuclear cell infiltration in the Virchow–Robin space, neuronal necrosis, vacuolization and neuronal degeneration, neuronophagy, and gliosis. An immunohistochemical analysis of tissues in the neural parenchyma showed significantly higher expression of the receptors NLRP1, NLRP3, and AIM2, cytokines IL-1β, IL-18, and IL-33, and enzymes caspase 1, iNOS, and arginase 1 in ZIKV-positive microcephaly cases than in flavivirus-negative controls. These results suggest that inflammasome activation can aggravate the neuroinflammatory response and consequently increase CNS damage in neonates with fetal neural ZIKV infection and microcephaly.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): S.M. Shamsul Islam, Bunsoon Choi, Juyoung Choi, Eun-So Lee, Seonghyang Sohn〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉It has been suggested higher serum levels of IL-15 and lower expression levels of IL-15 receptor alpha (IL-15Rα) are correlated with pathogenesis of Behçet's disease (BD). However, whether overexpressing IL-15Rα could be used as a therapeutic candidate for BD is currently unclear. Therefore, the purpose of this study was to determine whether overexpressing IL-15Rα could affect BD symptoms in a mouse model. IL-15/IL-15Rα complex expressing vector or protein complex of IL-15/IL-15Rα-Fc was used to treat BD mice. Frequencies of IL-15Rα+ cells in peripheral blood leukocytes (PBL) and lymph node cells were determined using a flow cytometer. BD symptoms in mice improved after treatment with IL-15/15Rα expression vector or IL-15/IL-15Rα-Fc protein complex. In addition, treatment with pIL-15/15Rα significantly (p = .016) decreased disease severity score of BD mice compared to treatment with control vector. Frequencies of IL-15Rα+ cells were also significantly (p = .01) higher in peritoneal macrophages of pIL-15/15Rα treated BD mice than those of mice treated with control vector. Frequencies of IL-15Rα+ PBL were also significantly higher in BD mice treated with IL-15/IL-15Rα-Fc protein complex than those in the control group. These results suggest up-regulating IL-15Rα+ cells could be used as novel therapeutic strategies to control BD in the future.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Pascale Garnier, Rosemary Mummery, Mark J. Forster, Barbara Mulloy, Roslyn V. Gibbs, Christopher C. Rider〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉We have previously shown that the heterodimeric cytokine interleukin-12, and the homodimer of its larger subunit p40, both bind to heparin and heparan sulfate with relatively high affinity. In the present study we characterised these interactions using a series of chemically modified heparins as competitive inhibitors. Human interleukin-12 and p40 homodimer show indistinguishable binding profiles with a panel of heparin derivatives, but that of murine interleukin-12 is distinct. Heparin markedly protects the human and murine p40 subunits, but not the p35 subunits, from cleavage by the bacterial endoprotease LysC, further implicating the larger subunit as the location of the heparin binding site. Moreover the essential role of the carboxyterminal D3 domain in heparin binding is established by the failure of a truncated construct of the p40 subunit lacking this domain to bind. Predictive docking calculations indicate that a cluster of basic residues at the tip of the exposed C′D′ loop within D3 is important in heparin binding. However since the human and murine C′D′ loops differ considerably in length, the mode and three dimensional orientation of heparin binding are likely to differ substantially between the human and murine p40s. Thus overall the binding of IL-12 via its p40 subunit to heparin-related polysaccharides of the extracellular matrix appears to be functionally important since it has been conserved across mammalian species despite this structural divergence.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1043466618301674-fx1.jpg" width="341" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Patrícia A.F. Ribeiro, Daniel S. Dias, Marcus V.M. Novais, Daniela P. Lage, Grasiele S.V. Tavares, Débora V.C. Mendonça, Jamil S. Oliveira, Miguel A. Chávez-Fumagalli, Bruno M. Roatt, Mariana C. Duarte, Daniel Menezes-Souza, Fernanda Ludolf, Carlos A.P. Tavares, Mônica C. Oliveira, Eduardo A.F. Coelho〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉〈em〉Leishmania〈/em〉 proteins have been evaluated as vaccine candidates against leishmaniasis; however, most antigens present low immunogenicity and need to be added with immune adjuvants. A low number of licensed adjuvants exist on the market today; therefore, research conducted to produce new products is desirable. The present study sought to evaluate the immunogenicity and protective efficacy of a recombinant 〈em〉Leishmania〈/em〉 hypothetical protein, namely LiHyR, administered with saponin or liposomes in BALB/c mice. Immunological and parasitological parameters were evaluated, and results showed significant protection against 〈em〉Leishmania infantum〈/em〉 infection produced by both compositions in the immunized animals; however, this was not identified when the antigen was used alone. In addition, the liposomal formulation was more effective in inducing a polarized Th1 response in the vaccinated animals, which was maintained after challenge and reflected by lower parasitism found in all evaluated organs when the limiting dilution technique and RT-PCR assay were employed. The protected animals showed higher levels of protein and parasite-specific IFN-γ IL-2, IL-12, GM-CSF, and TNF-α, which were evaluated by capture ELISA and flow cytometry, in addition to a higher production of anti-protein and anti-parasite IgG2a antibodies, both before and after challenge. The Lip/rLiHyR combination induced higher IFN-γ production through both CD4〈sup〉+〈/sup〉 and CD8〈sup〉+〈/sup〉 T cell subtypes. Results indicate the possibility of using the LiHyR, containing a liposomal formulation, as a vaccine candidate against visceral leishmaniasis.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1043466618303557-ga1.jpg" width="332" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Smriti K. Raychaudhuri, Christine Abria, Emanual Michael Maverakis, Siba P. Raychaudhuri〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Objective〈/h6〉 〈p〉Functions of the Th9 cells and its signature cytokine IL-9 in human autoimmune diseases is currently under extensive research. Here we are reporting new functions of IL-9-receptor (IL-9R); its regulatory role on (i) FLS (fibroblast like synoviocyte) biology and (ii) pannus formation in rheumatoid arthritis (RA) and psoriatic arthritis (PsA).〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉RA, PsA, and OA synovial tissue biopsies were obtained; FLS were derived and cultured from these tissues. T quantify protein and messenger RNA levels of IL9-receptor (IL-9R) Western blot and real-time PCR techniques were used. For Pro-growth/survival effect of IL-9 (rIL-9) Annexin-V (apoptosis assay) and MTT assays were used.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Immunoblot and RT-PCR studies demonstrated IL9-R in FLS of RA, PsA, and OA. IL9-R was functionally active. rIL-9 induced significant proliferation of FLS (p 〈 0.001) and had an inhibitory effect on TNF-α induced apoptosis. Proliferation of FLS induced by rIL-9 could be significantly inhibited (p 〈 0.001) with an IL-9R antibody. Further we observed, rIL-9 induced increased secretion of IL-6, IL-8 and also unregulated MMP-3 expression in FLS.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Proliferation of FLS, induction of pro-nflammatory cytokines and upregulation of metaloprotinase (MMP 3) the key pathologic events for pannus formation are regulated by IL-9 and its recptor. Thus the IL-9/IL-9R system is a new contributing factor in the cytokine network of PsA and RA.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): António Galvão, Karolina Wolodko, Maria Rosa Rebordão, Dariusz Skarzynski, Graça Ferreira-Dias〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In the present report we describe the involvement of transforming growth factor B1 (TGF) in functional regression and structural luteolysis in the mare. Firstly, TGF and its receptors activin-like kinase (ALK) 5 and TGF receptor 2 were identified in corpus luteum (CL) steroidogenic, endothelial and fibroblast-like cells. Also, TGF and ALK5 protein expression were shown to be increased in Mid-, and Late-CL (p 〈 0.05). Subsequently, using an 〈em〉in vitro〈/em〉 model with Mid-CL cells, we studied the role of TGF on secretory activity and cell viability. Cell treatment with TGF decreased progesterone (P4) and prostaglandin (PG) E2 concentrations in culture media (p 〈 0.05), and downregulated mRNA and protein of StAR, CYP11A1, cPGES and mPGES1 (p 〈 0.05). Conversely, TGF augmented PGF2a concentration in culture media, through PTGS2 and PGFS gene expression activation (p 〈 0.05). When cells were incubated with PGF2a, both TGF and ALK5 were upregulated (p 〈 0.05). Additionally, treatment with the pharmacological inhibitor of ALK5, ALK4 and ALK7 - SB431542 (SB) attenuated PGF2a functional and structural luteolytic actions. Indeed, SB blocked: (i) PGF2a inhibitory effect on StAR, CYP11A1, 3BHSD and mPGES1; (ii) PGF2a auto-amplification signal via PTGS2 and PGFS expression (p 〈 0.05); (iii) the PGF2a-induced BAX and FASL expression (p 〈 0.05). Finally, TGF decreased cell viability (p 〈 0.05) and promoted caspase 3 activity (p = 0.08) and the expression of pro-apoptotic FASL and BAX (p 〈 0.05). Our results suggest that TGF supports functional regression and structural luteolysis, and also confirm the importance of ALK5, ALK4 and ALK7 activation during PGF2a mediated luteolysis in mares.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Rafaela Pravato Colato, Vânia Brazão, Gabriel Tavares do Vale, Fabricia Helena Santello, Pedro Alexandre Sampaio, Carlos Renato Tirapelli, Gabriela Pereira-da-Silva, José Clóvis Do Prado〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Aging is linked with a thymic oxidative damage and some infectious diseases such as Chagas’ disease may aggravate this process. The aim of this study was to evaluate the production of distinct cytokines as well as the antioxidant/oxidant status of the thymus and thymocytes populations during 〈em〉Trypanosoma cruzi (T. cruzi)〈/em〉 infection. Young (5 weeks old) and aged (18 weeks old) male Wistar rats were inoculated with blood trypomastigotes forms of the Y strain of 〈em〉T. cruzi〈/em〉. On the 16th day after 〈em〉T. cruzi〈/em〉 infection, increased concentrations of transforming growth factor β (TGF-β), interleukin (IL)-12, IL-17 were detected in aged infected subjects as compared to young infected ones. Interestingly, a reduction in the production of tumor necrose factor (TNF)-α was observed in aged infected rats when compared to young infected subjects. Aged-infected rats presented increased O〈sub〉2〈/sub〉〈sup〉−〈/sup〉 levels, compared to young counterparts. Significant raise in the generation of O〈sub〉2〈/sub〉〈sup〉−〈/sup〉 in aged infected animals, as compared to uninfected counterparts was observed. Up-regulated expression of Nox2 in the thymus of young and aged infected animals was observed. An increased SOD2 expression was detected in the thymus of young animals infected with 〈em〉T. cruzi〈/em〉, when compared to uninfected young rats. Aged animals showed reduced thymus weight and the number of thymocytes. Decreased percentages of SPCD4〈sup〉+〈/sup〉 and SPCD8〈sup〉+〈/sup〉T cells were detected in aged and control groups when compared to young counterparts. In summary, this is the first data to directly examine the influence of aging on age-related dysfunctions during the acute phase of experimental Chagas disease. Concerning to oxidative stress, it is clear from our analysis that aged infected rats suffer a more intense oxidative damage when compared to young and infected ones. Age and infection triggered a dynamic interplay of cytokines, oxidative stress and thymic dysfunctions which led to impaired response from aged and infected rats. Such findings may have significant functional relevance in therapeutic strategies in order to reestablish the thymic immunological function which occurs in aged and 〈em〉T. cruzi〈/em〉 infected subjects.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Stephen B. Shears, Yoichi Hayakawa〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Our laboratories have determined that the 〈em〉Drosophila〈/em〉 cytokine, Growth-blocking peptide (GBP), mediates its biological effects through the Mthl10 G-protein coupled receptor. In this 〈em〉Cytokine Stimulus〈/em〉, we discuss the functional plasticity of the GBP/Mthl10 axis, and we propose that conserved components of this regulatory network may be relevant to human health.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Xiang Hu, Huamin Wang, Chaofeng Han, Xuetao Cao〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The balance between pro-inflammatory and anti-inflammatory macrophage generation, a process known as polarization, is critical for immune homoeostasis. Identifying the molecular mechanisms underlying polarization and the generation of anti-inflammatory macrophages is an area of high current interest. Our previous work has demonstrated that integrin CD11b promotes IL-10 production in macrophages by activating the Sarcoma gene (Src), yet whether and how Src modulates anti-inflammatory macrophages is not known. Here we show that Src inhibitor (Dasatinib)-treated mice were highly susceptible to dextran sulfate sodium (DSS)-induced colitis, with a much more sever inflammation response, accompanying by high TNF-α, and low IL-10 expression. Inhibition of Src enhanced the expression of pro-inflammatory macrophage marker inducible nitric oxide synthase (iNOS), but reduced the expression of anti-inflammatory macrophage marker arginase1 (Arg1) in both intestinal macrophages and bone marrow-derived macrophages (BMDMs). Overexpression of constitutively activated Src promoted IL-4-induced expression of Arg1 through STAT6 phosphorylation, and Jak1 was also involved in this process. Our results reveal that the IL-4-Src-STAT6 pathway plays a major role in polarizing anti-inflammatory macrophage generation and suggest a potential anti-inflammatory role for Src in inflammatory diseases.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Dominic Paquin-Proulx, Benjamin C. Greenspun, Shannon M. Kitchen, Rui André Saraiva Raposo, Douglas F. Nixon, Leon Grayfer〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The establishment of latent HIV-1 reservoirs in terminally differentiated cells represents a major impediment to the success of antiretroviral therapies. Notably, macrophages (Mϕs) are susceptible to HIV-1 infection and recent evidence suggests that they may be involved in long-term HIV-1 persistence. While the extensive functional heterogeneity seen across the Mϕ cell lineage parallels the spectrum of HIV-1 susceptibility reported across these cell subsets, the facets of Mϕ HIV-1 resistance and susceptibility remain to be fully defined. Notably, the differentiation of most Mϕ subsets depends on signaling through the macrophage colony-stimulating factor receptor (M-CSFR), which in addition to M-CSF, is now known to bind the unrelated interleukin-34 (IL-34) cytokine. The biological need for two M-CSFR ligands awaits full elucidation. Here, we report that Mϕs differentiated from human peripheral blood monocytes with IL-34 are substantially more resistant to HIV-1 infection than M-CSF-derived Mϕs. Moreover, while both Mϕ subsets express comparable surface protein levels of the HIV-1 receptor and co-receptor, CD4 and CCR5 respectively, the IL-34-Mϕs express significantly greater levels of pertinent restriction factor genes, potentially accounting for their greater resistance to HIV-1 infection than that observed in M-CSF-Mϕs. Together, our findings underline previously unexplored differentiation pathways resulting in HIV-1-susceptible and resistant Mϕ subsets and pave the way for further research that may overcome one of the last major hurdles in developing more successful antiretroviral therapy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Mehdi Tourani, Maryam Habibzadeh, Ahmad Karkhah, Javad Shokri-Shirvani, Ladan Barari, Hamid Reza Nouri〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Peptic ulcer is a lesion in the mucosa of the digestive tract affecting many people all around the world. Recent investigations have indicated that produced inflammatory cytokines such as TNF-α and IL-1β in response to gastric infection by 〈em〉Helicobacter pylori〈/em〉 play an important role in the development of peptic ulcer. With regard to the significance of these cytokines in peptic ulcer development and the high prevalence of this disease in the developing countries, this study aimed to investigate the association of TNF-α and IL-1β with peptic ulcer in the presence of 〈em〉H. pylori〈/em〉. This case-control study enrolled 61 patients with peptic ulcer disease (PUD) as cases and 59 people without peptic ulcer (NPUD) as controls. Blood samples and endoscopic biopsies were collected. 〈em〉H. pylori〈/em〉 infection was confirmed by using rapid urease test (RUT), specific IgG measurement and histopathological examination. Then, IL-1β and TNF-α levels were evaluated using enzyme linked immunosorbent assay (ELISA). The seropositivity of 〈em〉H. pylori〈/em〉 was 62.5% in the studied population, while by considering RUT and histopathological examination along with specific-IgG antibody, 〈em〉H. pylori〈/em〉 infection decreased to 56.7%. In addition, 〈em〉H. pylori〈/em〉 infection was significantly (OR = 0.37; 95% CI = 0.17–0.82; P = .02) associated with peptic ulcer development. The TNF-α level in PUD and infected 〈em〉H. pylori〈/em〉 subjects was significantly higher than that of control and un-infected 〈em〉H. pylori〈/em〉 individuals. However, no significant difference of IL1β level was observed between PUD and control groups as well as between 〈em〉H. pylori〈/em〉 infected and un-infected individuals. Interestingly, IL-1β level in PUD patients without 〈em〉H. pylori〈/em〉 infection was significantly higher than infected ones. Moreover, a significant correlation between specific-IgG antibody with TNF-α level was observed. Taken together, our results showed that increased level of TNF-α could probably play pivotal role in pathogenesis of peptic ulcer in the presence of 〈em〉H. pylori〈/em〉 infection. These findings also highlighted the importance of IL-1β in the absence of 〈em〉H. pylori〈/em〉 infection in peptic ulcer development.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Dajana F. Lendak, Dunja M. Mihajlović, Aleksandra S. Novakov-Mikić, Igor M. Mitić, Jasmina M. Boban, Snežana V. Brkić〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Members of TNFα superfamily, A proliferation inducing ligand (APRIL), B-cell activating factor (BAFF) and Transmembrane activator and calcium cyclophylin interactor (TACI) are main regulators of B-cell function. The aim of this study was to evaluate concentrations of APRIL, BAFF and soluble TACI (sTACI) receptor in septic patients compared to healthy controls and compare concentrations of these biomarkers depending on sepsis severity and outcome.〈/p〉 〈/div〉 〈div〉 〈h6〉Materials and methods〈/h6〉 〈p〉A total of 115 septic patients and 30 healthy volunteers were included and concentrations of APRIL, BAFF and sTACI were determined in all subjects at the admission (ELISA R&D Systems tests). Concentrations of these biomarkers in function of sepsis severity (sepsis n = 94 and septic shock n = 21) and outcome (lethal n = 40, recovery n = 75) were tested, as well as correlations with APACHE II and SOFA scores, immunoglobulins, complement, PCT and CRP concentrations.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Concentrations of all three biomarkers were significantly increased in septic patients compared to controls (AUC〈sub〉APRIL〈/sub〉 = 0.982, AUC〈sub〉BAFF〈/sub〉 = 0.873, AUC〈sub〉sTACI〈/sub〉 = 0.683). Higher concentrations of APRIL and sTACI (p = 0.033, p = 0.037), and lower concentrations of BAFF (p = 0.005) were observed in patients with septic shock compared to sepsis. BAFF concentrations correlated positively with IgM, C3 and C4 levels. sTACI and APRIL were shown to be predictors of lethal outcome (p = 0.003, p = 0.049).〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Concentrations of observed TNFα superfamily members are significantly increased in septic patients, confirming their role in sepsis pathogenesis. Higher concentrations of anti-inflammatory sTACI receptor correlated with severity of sepsis and poorer prognosis, thus potentially indicating domination of anti-inflammatory response in septic patients with worse outcome.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Juho Jalkanen, Olli Hautero, Mikael Maksimow, Sirpa Jalkanen, Harri Hakovirta〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Introduction〈/h6〉 〈p〉The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉The levels of VEGF (〈em〉P〈/em〉 = 0.009) and HGF (〈em〉P〈/em〉 〈 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (〈em〉P〈/em〉 = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson’s correlation = 0.183, 〈em〉P〈/em〉 = 0.004), HGF (Pearson’s correlation = 0.253, P 〈 0.001), bFGF (Pearson’s correlation = 0.169, P = 0.008) and PDGF (Pearson’s correlation = 0.296, P 〈 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson’s correlation −0.19, 〈em〉P〈/em〉 = 0.009) and TP (Pearson’s correlation −0.20, 〈em〉P〈/em〉 = 0.005) measurements.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Seok-Seong Kang, A. Reum Kim, Cheol-Heui Yun, Seung Hyun Han〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Secondary bacterial infection contributes to severe inflammation following viral infection. Among foodborne pathogenic bacteria, 〈em〉Staphylococcus aureus〈/em〉 is known to exacerbate severe inflammatory responses after infection with single-stranded RNA viruses such as influenza viruses. However, it has not been determined if 〈em〉S. aureus〈/em〉 infection enhances inflammatory responses after infection with RNA enteric viruses, including rotavirus, which is a double-stranded RNA virus. We therefore investigated the molecular mechanisms by which a cell wall component of 〈em〉S. aureus〈/em〉 enhanced inflammatory responses during enteric viral infection using poly I:C-primed macrophages, which is a well-established model for double-stranded RNA virus infection. 〈em〉S. aureus〈/em〉 lipoproteins enhanced IL-6 as well as TNF-α production in poly I:C-primed macrophages. Pam2CSK4, a mimic of Gram-positive bacterial lipoproteins and 〈em〉S. aureus〈/em〉 lipoproteins, also significantly enhanced IL-6 production in poly I:C-primed macrophages. While IFN-β expression was increased in poly I:C-primed macrophages treated with Pam2CSK4 or 〈em〉S. aureus〈/em〉 lipoproteins, the level of IL-6 enhancement in poly I:C-primed macrophages was decreased in the presence of anti-IFN-α/β receptor antibody, suggesting that IFN-β plays an important role in enhanced IL-6 production. Phosphatidylinositol-3-kinase, Akt, ERK and NF-κB were also involved in the enhanced IL-6 production. Collectively, these results suggest that 〈em〉S. aureus〈/em〉 lipoproteins induce excessive inflammatory responses in the presence of poly I:C.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Jun Ho Jeon, Deok-Bum Park, Sun-Je Woo, Hae-Ri Lee, Ok-Kyu Park, Jungchan Park, Gi-eun Rhie〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Poly-γ-〈span〉d〈/span〉-glutamic acid (PGA) of anthrax is an important pathogenic factor due to its anti-phagocytic activity. Additionally, PGA has the ability to activate mouse macrophages for the secretion of cytokines through Toll-like receptor (TLR) 2. Peptidoglycan (PGN), a major bacterial cell-wall component, induces inflammatory responses in the host. We assessed whether PGA can induce maturation and cytokine expression in immature mouse dendritic cells (DCs) in the existence of muramyl dipeptide (MDP), the minimum motif of PGN with immunostimulatory activity. Stimulation of immature DCs with PGA or MDP alone augmented expression of costimulatory molecules and MHC class II proteins, which are all cell surface markers indicative of maturation. The observed effects were further enhanced by costimulation of PGA and MDP. PGA alone was sufficient to induce expression of TNF-α, IL-6, MCP-1, and MIP1-α, whereas MDP alone did not under the same conditions. Treatment with MDP enhanced PGA-induced expression of the tested inflammatory mediators; however, the synergistic effect found for PGA and MDP was not observed in TLR2- or nucleotide-binding oligomerization domain (NOD) 2–knockout DCs. Additionally, MDP augmented PGA-induced MAP kinases and NF-κB activation, which is crucial for expression of cytokines. Furthermore, MAP kinase and NF-κB inhibitors attenuated MDP enhancement of PGA-induced cytokine production. In addition, co-culture of splenocytes and PGA/MDP-matured DCs induced higher expression of IL-2 and IFN-γ compared to that of splenocytes and PGA-matured DCs. Collectively, our results suggest that PGA and MDP cooperatively induce inflammatory responses in mouse DCs through TLR2 and NOD2 via MAP kinase and NF-κB pathways, subsequently leading to lymphocyte activation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Jameson K. Gardner, Melissa M. Herbst-Kralovetz〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Herpes simplex virus 2 (HSV-2) causes a persistent, lifelong infection that increases risk for sexually transmitted infection acquisition. Both the lack of a vaccine and the need for chronic suppressive therapies to control infection presents the need to further understand immune mechanisms in response to acute HSV-2 infection. The IL-36 cytokines are recently identified members of the IL-1 family and function as inflammatory mediators at epithelial sites. Here, we first used a well-characterized three-dimensional (3-D) human vaginal epithelial cell (VEC) model to understand the role of IL-36γ in the context of HSV-2 infection. In 3-D VEC, IL-36γ is induced by HSV-2 infection, and pretreatment with exogenous IL-36γ significantly reduced HSV-2 replication. To assess the impact of IL-36γ treatment on HSV-2 disease pathogenesis, we employed a lethal genital infection model. We showed that IL-36γ treatment in mice prior to lethal intravaginal challenge significantly limited vaginal viral replication, delayed disease onset, decreased disease severity, and significantly increased survival. We demonstrated that IL-36γ treatment transiently induced pro-inflammatory cytokines, chemokines, and antimicrobial peptides in murine lower female reproductive tract (FRT) tissue and vaginal lavages. Induction of the chemokines CCL20 and KC in IL-36γ treated mice also corresponded with increased polymorphonuclear (PMN) leukocyte infiltration observed in vaginal smears. Altogether, these studies demonstrate that IL-36γ drives the transient production of immune mediators and promotes PMN recruitment in the vaginal microenvironment that increases resistance to HSV-2 infection and disease. Our data indicate that IL-36γ may participate as a key player in host defense mechanisms against invading pathogens in the FRT.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 113〈/p〉 〈p〉Author(s): Pijun Yan, Yong Xu, Zhihong Zhang, Chenlin Gao, Jianhua Zhu, Hua Li, Qin Wan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Neuregulin-4 (Nrg4) is a novel adipokine associated with obesity, hyperglycemia, insulin resistance, dislipidemia, inflammation, and oxidative stress in mice and humans. However, no report has demonstrated the relationship of circulating Nrg4 with diabetic peripheral neuropathy (DPN). The objective of our study was to investigate the relationship between circulating Nrg4 and DPN in a cross-sectional study. Circulating Nrg4 levels were determined with an enzyme-linked immunosorbent assays kit in 132 newly diagnosed type 2 diabetes mellitus (nT2DM) patients and 41 normal controls (NC group). The associations of circulating Nrg4 with other parameters were also analyzed. Circulating Nrg4 levels were significantly lower in nT2DM patients with no DPN than in NC subjects, and were further markedly decreased in nT2DM patients with DPN (〈em〉P〈/em〉 〈 0.01 or 〈em〉P〈/em〉 〈 0.05). Circulating Nrg4 levels were progressively decreased with an increasing number of abnormal DPN screening (〈em〉P〈/em〉 for trend 〈 0.01). Circulating Nrg4 levels correlated negatively with 8-iso-prostaglandin F〈sub〉2α〈/sub〉 (8-iso-PGF〈sub〉2α〈/sub〉), high-sensitivity C-reactive protein (hs-CRP) and vibration perception threshold (VPT) (all 〈em〉P〈/em〉 〈 0.01), and 8-iso-PGF〈sub〉2α〈/sub〉, hs-CRP, glycated hemoglobin A1c and VPT were independently related factors to circulating Nrg4 in nT2DM patients (〈em〉P〈/em〉 〈 0.01 or 〈em〉P〈/em〉 〈 0.05). Moreover, circulating Nrg4 was significantly associated with the development of DPN even after controlling for anthropometric, biochemical and clinical parameters. Additionally, the analysis of receiver operating characteristic curves revealed that the best cutoff value for circulating Nrg4 to predict DPN was 1.58 ng/mL (sensitivity 90.91%, specificity 54.55%, and area under the curve 0.716). These findings together suggested that circulating Nrg4 levels were reduced in DPN patients and Nrg4 may be a novel adipokine associated with inflammation, oxidative stress, and long-term glycemic control in nT2DM patients.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Kazuhisa Furue, Takamichi Ito, Masutaka Furue〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Psoriasis and psoriatic arthritis cause significant physical and psychological burdens for afflicted individuals. An accelerated TNF-α/IL-23/IL-17 axis is their major pathomechanism; therefore, anti-TNF-α/IL-23/IL-17 biologics are very effective for the treatment of skin and joint lesions in psoriasis and psoriatic arthritis. Given that the IL-17 signature is more upregulated in the skin than in synovium in psoriatic arthritis, anti-IL-23/IL-17 agents seem to be superior to anti-TNF-α remedies in the treatment of skin lesions. In this review, we focus on the differential efficacy of anti-TNF-α/IL-23/IL-17 biologics in psoriasis and psoriatic arthritis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Sarita Kumari, Pushkar Shivam, Shashank Kumar, Fauzia Jamal, Manish Kumar Singh, Sanjiva Bimal, Shyam Narayan, Krishna Pandey, Vidya Nand Ravi Das, Pradeep Das, Shubhankar K. Singh〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Sterile cure from visceralized 〈em〉Leishmania donovani〈/em〉 (〈em〉L. donovani〈/em〉) needs Th1 cell support along with the assistance from innate immune cells, NK cells and NKT cells. NKT cells play as a connecting link between innate and adaptive immune cell and support T helper cell function. Earlier, a categorical function of CD56 positive CD4〈sup〉+〈/sup〉 or CD8〈sup〉+〈/sup〉 NKT cells was reported in visceral leishmaniasis (VL). It was observed in 〈em〉in vitro〈/em〉 that CD4〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells, but not CD8〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells, were accumulated at the 〈em〉L. donovani〈/em〉 infection site. Therefore, 〈em〉in vitro〈/em〉 experiments have been carried out to decipher the mechanism behind preferential accumulation of CD4〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells at infection site. In this study, 1.89 fold higher expression of CCL4/MIP-1β was noticed in infected macrophages. The higher expression of CCL4 was correlated with preferential accumulation of CCR5〈sup〉+〈/sup〉CD4〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells and apoptosis of CD8〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells at 〈em〉in vitro〈/em〉 infection site. The CD4〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells were also observed expressing TGF-β dominantly. Interaction of CCL4 chemotaxis was interrupted by blocking, which led to drift back the TGF-β producing CD4〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells and promoted CD8〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells recruitment in 〈em〉in vitro〈/em〉 infection site. CCR5 blockade also reduced CD25 and FoxP3 positive CD4〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells in 〈em〉in vitro〈/em〉 infection site. Therefore, it was concluded that 〈em〉Leishmania〈/em〉 promotes strategic expression of CCL4, which alternately attracts CCR5〈sup〉+〈/sup〉 cells, mostly expressing regulatory cytokines, at infection site. This reduces the CD8〈sup〉+〈/sup〉CD56〈sup〉+〈/sup〉NKT cells at infection site through Smad4 mediated TGF-β expression and activation of caspases. Data indicates that 〈em〉L. donovani〈/em〉 induces higher expression of CCL4 in host cell to attract CCR5〈sup〉+〈/sup〉 cells under its strategic plan to downregulate host immune response.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Wael Alturaiki, Amanda J. McFarlane, Katie Rose, Rachel Corkhill, Paul S. McNamara, Jürgen Schwarze, Brian F. Flanagan〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection. Following infection with A2 strain RSV, the highest RSV N gene expression was observed at day 4 after challenge with virus. In contrast, two peaks of elevated BAFF expression at days 2 and 7 were observed. CXCL13 was significantly elevated at days 1, 2 and 7. CXCL12, CCL19 and CCL21 were expressed within lung tissue from control and RSV challenged animals but no significant difference in expression was found. Immunofluorescence showed BAFF to be present throughout the tissue however CXCL13 expression was localized to cell rich areas probably constituting lymphoid aggregates. Our results define the kinetics of B cell chemoattractant and growth factor expression during RSV infection and indicate an important role for these cytokines in the airway response to RSV infection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): M. Elhamouly, T. Nii, N. Isobe, Y. Yoshimura〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The aim of this study was to examine whether cytokines and chemokines expressed in the uterine mucosa play a role in the process of eggshell formation in the chicken uterus. Changes in the expression levels of pro- and anti-inflammatory cytokines and chemokines in the uterine mucosa during an ovulatory cycle (experiment 1) and effects of aging on their expression (experiment 2) were examined. In experiment 1, the expression of the pro-inflammatory cytokines 〈em〉IL1β〈/em〉, 〈em〉IL6〈/em〉, 〈em〉TNFSF15〈/em〉, and 〈em〉IFNγ〈/em〉, and a chemokine 〈em〉CX3CL1〈/em〉 was found to increase during eggshell biomineralization (16 h following oviposition), while anti-inflammatory 〈em〉TGFβ2〈/em〉 expression was found to increase at 4 h following oviposition. In experiment 2, a higher expression of the anti-inflammatory cytokines 〈em〉TGFβ2〈/em〉 and 〈em〉TGFβ3〈/em〉, and chemokines 〈em〉CXCLi2〈/em〉 and 〈em〉CX3CL1〈/em〉, was observed in aged hens than in young hens. A significantly higher number of macrophages and CD8+ T cells were observed in the uterine tissue of aged hens than in young hens. Furthermore, the expression of adhesion molecules associated with leukocytic infiltration was found to be higher in aged hens than in young hens. We conclude that the eggshell formation process may be affected by the pro- and anti-inflammatory cytokines and chemokines. The balanced expressions of these molecules might be disrupted in aged hens.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Anna Lehmann-Kalata, Izabela Miechowicz, Katarzyna Korybalska, Ewelina Swora-Cwynar, Natasza Czepulis, Joanna Łuczak, Zofia Orzechowska, Marian Grzymisławski, Anna Surdacka, Janusz Witowski〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉The nature of a link between poor oral health and obesity is not fully understood. It is also unclear if saliva contributes to it and whether the properties of saliva change as a result of an increase in body mass or rather as a consequence of obesity-associated comorbidities. This pilot study was undertaken in an attempt to determine if salivary biomarkers can identify obesity per se.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Whole mixed saliva was analysed for 16 soluble parameters covering 4 categories (inflammation, oxidative stress, endothelial dysfunction, adipokines). In the discovery group, 19 obese and 25 non-obese women matched for age, with similar hygiene habits, with no comorbidities and not taking any medication known to affect saliva secretion were analysed. In the validation group, a cohort of no-preselected 81 individuals (34 obese) were analysed.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Individuals with obesity had significantly higher salivary concentrations of several cytokines and adipokines, of which TNF-R1, serpin A12 and PAI-1 were identified as parameters discriminating between obese and non-obese subjects with the highest sensitivity and specificity.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Obesity per se leads to distinct changes in the concentration of several parameters in saliva. These findings may have diagnostic implications for distinguishing the effects of obesity and obesity-linked comorbidities on oral health.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Renato Mastrangeli, Wolf Palinsky, Horst Bierau〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉All type I interferons share structural homology and bind to a common heterodimeric receptor consisting of the IFNAR1 and IFNAR2 subunits, which are expressed on most cell types. Although binding to the same receptor pair, they evoke a broad range of activities within the cell affecting the expression of numerous genes and resulting in profound cellular changes. Differential activation results from multiple levels of cellular and molecular events including binding affinity, receptor density, cell type-specific variations, and post-translational modification of signaling molecules downstream. Within the type I interferon family the Asn-Gly-Arg (NGR) sequence motif is unique to interferon-β and, together with its deamidated variants Asp-Gly-Arg (DGR) and iso-Asp-Gly-Arg (iso-DGR), imparts additional binding specificities that go beyond that of the canonical IFNAR1/IFNAR2. These warrant further investigations and functional studies and may eventually shed new light on differential effects observed for this molecule in oncology and autoimmune diseases.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Xiaojie Huang, Linyan Jia, Zhen Qian, Yuanhui Jia, Xiao Chen, Xianghong Xu, Xinwen Chang, Ming Liu, Kai Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Angiogenesis is fundamental to normal placental development, and aberrant angiogenesis contributes substantially to placental pathologies. Placental angiogenesis is a pivotal process that plays a key mechanistic role in the elaboration of the placental villous tree, which is mainly taken by human placental microvascular endothelial cells (HPMECs), present in the fetal capillaries of chorionic villi, and macrovascular human umbilical vein endothelial cells (HUVECs) also play a role in this process. These are the two types of endothelial cells that form the placenta and differ in morphology and function. The placental vasculature represents a distinct territory that is highly specialized in structure and function. To distinguish the differences between HPMECs and HUVECs, we isolated HPMECs by paramagnetic particle separation and HUVECs through trypsinization and validated their characteristics. Then, we examined their response to fibroblast growth factor 2 (FGF2), vascular endothelial growth factor (VEGF) and endocrine-gland-derived vascular endothelial growth factor (EG-VEGF), as well as the underlying signaling mechanisms and their transcriptomes. We found that cultured HPMECs and HUVECs took up DiI-Ac-LDL and formed capillary-like tube structures on Matrigel. HPMECs and HUVECs had different expressions of eNOS, PROKR1 and PROKR2, and these characteristics substantiate the endothelial nature of cultured cells. FGF2 and VEGF stimulated the proliferation and migration of HPMECs and HUVECs via activation of PI3K/AKT1 and MEK1/MEK2/ERK1/ERK2. Interestingly, EG-VEGF increased the proliferation and migration of HPMECs via only MEK1/MEK2/ERK1/ERK2 and not PI3K/AKT1. Microarray analysis showed that there were some differentially expressed genes between HPMECs and HUVECs. Gene ontology analysis indicated that the differentially expressed genes were highly related to G-protein coupled receptor signaling pathway, angiogenesis, L-lysine transmembrane transport and blood vessel remodeling. These data provided evidence of heterogeneity between microvascular HPMECs and macrovascular HUVECs that most likely reflected significant differences in endothelial cell function in the two different cellular environments.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Yi Zhang, Peiyi Lin, Cheng Hong, Qian Jiang, Yue Xing, Xiaoyan Tang, Huilin Jiang, Shuhong Luo, Xiaohui Chen〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) and is a significant risk factor for hospitalization and shortened life expectancy. Therefore, developing new serum biomarkers for early diagnosis and prognosis of COPD associated PH is crucial. In the present study, a solid-phase antibody array simultaneously detecting multiple proteins was used to search specific COPD associated PH biomarkers, with COPD patients and healthy subjects as control groups. As a result, compared to the COPD and healthy groups, the levels of MCP-4, SDF-1 alpha, CCL28, Adipsin, IL-28A, CD40 and AgRP were uniquely altered in COPD patient serum with pulmonary hypertension. Among these proteins, CCL28, MCP-4, CD40, AgRP and IL-28A were identified to be differentially expressed in COPD patients with hypertension, indicating that these cytokines may serve as novel biomarkers for the diagnosis and prognosis of COPD associated pulmonary hypertension.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Nelson G. Oliveira-Júnior, Mirna S. Freire, Jeeser A. Almeida, Taia M.B. Rezende, Octávio L. Franco〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Hospital infections allied to bacterial resistance to antibiotics have become a major worldwide problem. In this context, antimicrobial peptides (AMPs) are presented as an alternative in the control of these resistant organisms. Besides antimicrobial effects, these molecules play a crucial role in immunity by acting as immunomodulators. These peptides can activate inflammatory cells to produce pro- and anti-inflammatory mediators. In this study we will show the activity against multi-drug resistant bacteria (MDRB) of two cathelicidins from South American pit vipers 〈em〉Bothrops atrox〈/em〉 and 〈em〉Crotalus durissus terrificus,〈/em〉 named batroxicidin and crotalicidin. It was observed that both peptides showed activity against MDRB and presented no hemolytic or cytotoxic activity. In addition, the ability of peptides to modulate the production of cytokines TNF-α, IL-10 and IL-6 was analyzed using Raw 264.7 cells in the presence of IFN-γ stimuli, and multi-resistant 〈em〉E. coli〈/em〉 and 〈em〉K. pneumoniae〈/em〉 antigens. An up-expression or down-expression of TNF-α, as well as the IL-10 mediator, was observed. The cytokine IL-6, on the other hand, presented only a down-regulation for Raw 264.7 cell groups. In conclusion, the results demonstrate that both peptides presented a predominantly proinflammatory characteristic to the inflammatory mediators dosed. Overall, even presenting a proinflammatory characteristic, these peptides are still promising for future research and development of new potential antimicrobial molecules.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1043466618303788-ga1.jpg" width="286" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Simone Corrêa-Silva, Aline P. Alencar, Jusciele B. Moreli, Alexandre U. Borbely, Larissa de S. Lima, Cristóforo Scavone, Débora C. Damasceno, Marilza V.C. Rudge, Estela Bevilacqua, Iracema M.P. Calderon〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study was based on the hypothesis that IL-1β and its central regulator, the inflammasome, may play a role in the inflammatory condition exhibited by placental tissues from mothers with different gestational hyperglycemia levels. Pregnant women were classified according to the glycemic reference as non-diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift assay) and inflammasome protein expression (by Western blot) in chorionic villous. Maternal plasma and placental levels of inflammatory factors (IL-1β, IL-6, and MCP-1) were increased during all hyperglycemic conditions. Villous stroma cells showed strong immunoreactivity to CD68. In addition, with syncytiotrophoblast, the villous stroma cells were also stained to detect iNOS, MCP-1, TLR2, and TLR4. Although the levels of protein had fluctuated in the groups, NLRP1, NLRP3, ASC, and Caspase 1 were up-regulated in all hyperglycemic groups suggesting the inflammasome may be assembled in these pregnant women. The NFKB activity also exhibited higher levels in hyperglycemic groups, which might imply in pro-inflammatory cytokines production. In summary, increased maternal glucose levels during pregnancy changed systemic and placental inflammatory patterns, which occurred in parallel with the expression of inflammasome factors and processing and secretion of the pro-inflammatory cytokine IL-1β. These results suggest an inflammatory condition in all gestational hyperglycemic conditions, even in hyperglycemia that is less severe than gestational or overt diabetes, likely associated with inflammasome activation and inflammatory cytokine secretion. Inflammasome activation as a possible source of inflammatory factors may be an important target to be considered while managing hyperglycemia and preventing adverse pregnancy outcomes.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Felicitas Bucher, Jungho Lee, Sanghee Shin, Minseok S. Kim, Yong-Seok Oh, Sanghoon Ha, Hongkai Zhang, Kyungmoo Yea〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Interleukin-5 (IL-5) is best known as key regulator in eosinophil-associated diseases such as asthma. While a connection to vascular changes in eosinophil-associated lung diseases is still elusive, recent evidence suggests that IL-5 may have an atheroprotective role. Here, we report an unexpected anti-angiogenic potential of IL-5 on vascular endothelial cells 〈em〉in vitro〈/em〉. IL-5 significantly inhibited fundamental functions of human lung microvascular endothelial cells (HMVEC-L) in vessel formation including VEGF-induced endothelial cell proliferation, migration and tube formation. Knockdown (KD) of STAT5 abolished the direct anti-angiogenic effect of IL-5 on VEGF-induced endothelial cell proliferation, migration and tube formation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Xingmu Wang, Feiying Yang, Guangen Xu, Shuping Zhong〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Recently, the roles of interleukin-6 (IL-6), IL-8 and IL-10 gene polymorphisms in gastric cancer have been extensively studied, with conflicting results. Therefore, we conducted the present study to better assess the potential correlations between these interleukin gene polymorphisms and gastric cancer.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Eligible articles were searched in PubMed, Medline, Embase, Web of Science and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential associations between interleukin gene polymorphisms and the risk of gastric cancer.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉A total of 73 case-control studies were finally included. Significant associations with the risk of gastric cancer were only detected for the IL-8 rs4073 polymorphism in overall analyses. Further subgroup analyses according to ethnicity of participants revealed that the IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896 polymorphisms were all significantly associated with the risk of gastric cancer in Asians. No positive results were found for any investigated interleukin gene polymorphisms in Caucasians.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Our findings suggest that IL-6 rs1800796, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896 polymorphisms may serve as genetic biomarkers of gastric cancer in Asians.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Xin Yi, Jinxue Zhang, Ran Zhuang, Song Wang, Shiyang Cheng, Dongliang Zhang, Jiangang Xie, Wei Hu, Xueqin Liu, Yun Zhang, Yong Ding, Yuan Zhang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Formation of macrophage-derived foam cells may mark the initial stages of atherosclerosis. We investigated the association between the expression of the leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) in macrophages and foam cell formation. A foam cell model was established by incubating THP-1-derived macrophages and bone marrow macrophages (BMMs) with oxidized low-density lipoprotein (ox-LDL). The role of LAIR-1 in foam cell formation was evaluated via Oil Red O staining and Dil-ox-LDL fluorescence intensities. Peroxisome proliferator-activated receptor gamma (PPARγ), cholesterol metabolism-related genes, and the role of LAIR-1 in activating classically activated (M1) and alternatively activated (M2) macrophages were evaluated by qPCR. Additionally, activation of protein-tyrosine phosphatase-1 (SHP-1) and cAMP-response element binding protein (CREB) were detected by western blotting. Results indicated that silencing LAIR-1 in macrophages modulated the SHP-1/CREB/PPARγ pathway, thereby promoting M2 macrophage polarization and increasing foam cell formation. Therefore, Inhibition of LAIR-1 in macrophages may promote foam cell formation and atherosclerosis.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1043466618303636-ga1.jpg" width="403" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Bi Li, Jing Fang, Zhicai Zuo, Sirui Yin, Tingting He, Mingxian Yang, Junliang Deng, Liuhong Shen, Xiaoping Ma, Shumin Yu, Ya Wang, Zhihua Ren, Hengmin Cui〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Resistin, a previously discovered cysteine-rich adipokine known to regulate glucose metabolism, has been emerged as a mediator in inflammation and immunity. Its level was supposed to be related to the expression of indicators, such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in inflammation. Toll-like receptor 4 (TLR4) was reported to be a receptor for resistin in cells, like leukocytes and peripheral blood mononuclear cells (PBMC). However, the pro-inflammatory role of resistin and its intracellular mechanisms in alveolar macrophages have not been thoroughly validated. Here we found that the pro-inflammatory cytokine expression in porcine alveolar macrophages (PAMs) was positively correlated with resistin. Our results also showed that resistin induced the expression of TLR4, intracellular molecules myeloid differentiation primary response protein 88 (MyD88), TRIF-related adaptor molecule (TRAM) and nuclear factor κB (NF-κB) in PAMs. In contrast, inhibition of TLR4, MyD88, TRAM and NF-κB abrogated the pro-inflammatory effect of resistin on PAMs. Additionally, the associations among TLR4, MyD88/TRAM and NF-κB were investigated by introducing TLR4-siRNA, MyD88-siRNA and TRAM-siRNA respectively into PAMs prior to the treatment with resistin. Taken together, our findings demonstrated that resistin promoted the production of pro-inflammatory cytokine in PAMs via TLR4/NF-κB-mediated pathway (TLR4/MyD88/TRAM/NF-κB).〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Zhengxiang He, Lili Chen, Glaucia C. Furtado, Sergio A. Lira〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Interleukin 33 (IL33) is a cytokine found in the extracellular space (mature IL33) or in the cell nucleus (full-length IL33). Nuclear accumulation of IL33 has been reported in intestinal epithelial cells (IEC) during intestinal inflammation and cancer, but a functional role for this nuclear form remains unclear. To study the role of nuclear IL33 in IEC, we generated transgenic mice expressing full-length IL33 in the intestinal epithelium (〈em〉Vfl33〈/em〉 mice). Expression of full-length IL33 in the epithelium resulted in accumulation of IL33 protein in the nucleus and secretion of IL33. Over-expression of full-length IL33 by IEC did not promote gut inflammation, but induced expression of genes in the IEC and lamina propria lymphocytes (LPL) that correlated negatively with genes expressed in inflammatory bowel diseases (IBD). Because the IL33 receptor ST2 is expressed by IEC, there was the potential that both the mature and full-length forms could mediate this effect. To specifically interrogate the transcriptional role of nuclear IL33, we intercrossed the 〈em〉Vfl33〈/em〉 mice with ST2- deficient mice. ST2 deficiency completely abrogated the transcriptional effects elicited by IL33 expression, suggesting that the transcriptional effects of IL33 on IEC are mediated by its mature, not its nuclear form.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Guo-hui Yang, Chi Zhang, Nan Wang, Yu Meng, Yi-sheng Wang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Anacardic acid, which is abundant in nutshell of 〈em〉Anacardium occidentale〈/em〉, has multiple pharmacological activities. In this study, we examined the therapeutic potential of anacardic acid in treating rheumatoid arthritis (RA). We explored the effects of anacardic acid on collagen-induced arthritis (CIA) in mice and on the proliferation and invasion of RA fibroblast-like synoviocytes (RA-FLSs). The underlying molecular mechanism was investigated. Anacardic acid treatment markedly suppressed paw swelling, joint destruction, and arthritis scores in CIA mice. The serum levels of tumor necrosis factor alpha (TNF- α) and interleutkin-1beta (IL- 1β) were significantly lowered by anacardic acid. 〈em〉In vitro〈/em〉 assays demonstrated that anacardic acid impaired the proliferation and invasion abilities of RA-FLSs in the presence of TNF- α or IL- 1β. Western blot analysis revealed the reduction of Akt protein expression and phoshporylation in RA-FLSs by anacardic acid. However, the mRNA level of Akt remained unchanged. Anacardic acid treatment significantly increased the expression of miR-633 in RA-FLSs. Akt was identified as a novel target of miR-633. Overexpression of miR-633 significantly inhibited the proliferation and invasion of RA-FLSs, which was rescued by enforced expression of Akt. Depletion of miR-633 prevented anacardic acid-mediated suppression of proliferation and invasion of RA-FLSs, which was accompanied by increased expression of Akt protein. In conclusion, anacardic acid may serve as a promising agent in the treatment of RA.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 113〈/p〉 〈p〉Author(s): Farimah Beheshti, Milad Hashemzehi, Nona Sabeti, Susan Hashemi Sadr, Mahmoud Hosseini〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Introduction〈/h6〉 〈p〉In the present study, the effects of aminoguanidine (AMG) on hippocampal cytokines, amyloid beta (Aβ), brain-derived neurotrophic factor, oxidative stress status and memory in chronically lipopolysaccharide (LPS) treated rats were investigated.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉The rats were divided into five groups and were treated: (1) Control (Saline), (2) LPS (1 mg/kg), (3–5) LPS- AMG50, LPS-AMG100, and LPS-AMG150 (AMG 50, 100 and 150 mg/kg 30 min before LPS injection). The treatment started five weeks prior to the behavioral experiments and continued during the behavioral tests (LPS injection two hours before each behavioral evaluation). Finally, the tissue was removed for biochemical measurements.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉The escape latency in Morris water maze test and the latency to enter the dark compartment in passive avoidance test in LPS group were significantly greater than the control group (P 〈 0.001), while, in LPS-AMG 100 and LPS-AMG150 groups they were less than LPS group (P 〈 0.001). Malondialdehyde (MDA), NO metabolites of hippocampal and cortical tissues and interleukin-6 (IL-6), Aβ and tumor necrosis factor-α (TNFα) concentration in the hippocampus of LPS group were higher than control group (P 〈 0.001-P 〈 0.05). However, in LPS-AMG 100 and LPS-AMG150 group they were lower than LPS group (P 〈 0.001-P 〈 0.05). The thiol content and the activities of catalase (CAT) and superoxide dismutase (SOD) in both cortical and hippocampal tissues of LPS group were reduced compared to the control group (P 〈 0.001-P 〈 0.05). These factors enhanced in LPS-AMG 100 and LPS-AMG150 groups compared to LPS (P 〈 0.001-P 〈 0.05). The hippocampal content of brain-derived neurotrophic factor (BDNF) in LPS group was significantly lower compared to the control group (P 〈 0.001). All treated groups had higher BDNF content in comparison to LPS group (P 〈 0.01-P 〈 0.001).〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉The findings indicated that the protective effects of AMG against LPS-induced memory were accompanied by decreasing of inflammatory cytokines, Aβ, oxidative stress and increasing of anti-inflammatory mediators and BDNF.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Azza M. Kamel, Abdallah Gameel, Gamal T.A. Ebid, Eman R. Radwan, Mostafa F. Mohammed Saleh, Raafat Abdelfattah〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem cell transplantation (HSCT); cytokines are recognized as important mediators in its pathogenesis. In this study we investigated the role of cytokine gene polymorphisms on HSCT outcome. A total of 106 patient and 98 donors were genotyped by polymerase chain reaction sequence specific primers (PCR-SSP) based assay for 〈em〉tumor necrosis factor-α−308 (TNFα -308), interleukin (IL)-6〈/em〉-〈em〉174, IL-10〈/em〉-〈em〉1082, −819, −592, Interferon-γ+874〈/em〉 (〈em〉IFN-γ+874〈/em〉), and 〈em〉transforming growth factor-β1 (TGF-β1〈/em〉) 〈em〉codon10 and 25〈/em〉 polymorphisms. Except one in each category, all patients and donors were 〈em〉TNFα〈/em〉 -308 high producers and the majority were 〈em〉IL-6〈/em〉-174 high producers (93.3% and 90.8% respectively); a pattern that would alleviate any potential biological impact. Patient's 〈em〉IFN-γ+〈/em〉874 showed significant association with the development of chronic GVHD. Patients with 〈em〉IFN-γ〈/em〉 +874 high producer showed an 8 folds likelihood to develop chronic GVHD as compared to those with 〈em〉IFN-γ〈/em〉+874 low producer predicted phenotype (95% CI: 1.59-40.2, p = 0.01). Patient's 〈em〉TGFβ〈/em〉1-codon 10 and 25 high/intermediate producers showed a lower incidence of acute GVHD though it did not achieve statistical significance (p = 0.065) on account of the low frequency of this genotype in our patients and donors (11.4 and 8.2% respectively). Other factors contributing to risk of GVHD included older age for both acute and chronic (p = 0.01 and 0.02 respectively) with age 24 as the best discriminating cutoff; CD34+ cell dose for chronic GVHD (p = 0.045) with a dose of 8 × 10〈sup〉6〈/sup〉/kg as the best discriminating cutoff; and conditioning regimen with Flu/Bu associated with the lowest incidence of acute GVHD (p = 0.003) and no impact on chronic GVHD. In conclusion the current study further indicates a potential role of some cytokine gene polymorphisms in the development of GVHD. The relative distribution of high and low producer genotypes in different ethnic groups contributes to their biological impact in different populations.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Mehrdokht Mazdeh, Mir Davood Omrani, Arezou Sayad, Alierza Komaki, Shahram Arsang-Jang, Mohammad Taheri, Soudeh Ghafouri-Fard〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Epilepsy is a chronic disorder in which immune dysregulation is shown to be involved. Imbalances in the cytokine levels both in serum and brain tissue have been demonstrated in epileptic patients. In the present study, we assessed mRNA expression of TNF-α, TGF-β, IFN-γ, CXCL8, IL-1β, IL-2, 1L-4, IL-6, IL-17 and CXCL8 in blood samples of 40 epileptic patients compared with age- and sex-matched healthy controls by means of quantitative real time PCR. The relative levels of CXCL8 transcripts were significantly higher in total epileptic patients compared with healthy subjects (P = .023). Relative mRNA expression of IFN-γ was significantly higher in female patients compared with female healthy subject (P = .048). In addition, significant correlations have been found between the mRNA levels of mentioned cytokines. Such imbalance between expression of pro-inflammatory and anti-inflammatory cytokines might be implicated in the pathogenesis of epilepsy.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Xiaolin Li, Tong Wu, Yongjun Jiang, Zining Zhang, Xiaoxu Han, Wenqing Geng, Haibo Ding, Jing Kang, Qi Wang, Hong Shang〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Objectives〈/h6〉 〈p〉The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC–MS).〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉A total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4 + T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Metabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Alessandro P. Delitala, Maristella Steri, Edoardo Fiorillo, Michele Marongiu, Edward G. Lakatta, David Schlessinger, Francesco Cucca〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Objective〈/h6〉 〈p〉Cytokines release by adipocytes could interact with TSH secretion. We evaluated the relationship between adipocytokines and TSH. We further tested for association of cytokines and thyroid autoimmunity.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉We conducted a cross-sectional study in a community-based sample including 5385 individuals (2964 female) with TSH within the reference range. Subjects who reported taking thyroid medications or drugs that alter thyroid function were excluded. TSH, FT4, adiponectin, leptin, antibody against thyroperoxidase and against thyroglobulin were measured. Linear and logistic regression models were used to test for association.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Females had higher adiponectin and leptin level and increased frequency of thyroid antibodies. In multiple regression analysis TSH was directly associated with leptin (β = 0.003, p = 0.001) and the presence of circulating antibody against thyroperoxidase (β = 0.315, p 〈 0.001), but negatively associated with age (β = −0.012, p 〈 0.001) and FT4 (β = −0.359, p 〈 0.001). Adiponectin, the presence of antibody against thyroglobulin and smoking habit were not associated with TSH levels (p = 0.223, p = 0.174 and p = 0.788, respectively). Logistic regression analysis revealed that higher adiponectin levels were associated with thyroid autoimmunity.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉Leptin is positively associated with TSH levels in euthyroid individuals, suggesting an effect of the adipokine on TSH secretion. Our results support the hypothesis that the leptin and pituitary-thyroid axis might interact in the context of energy homeostasis. The effect of adiponectin on thyroid autoimmunity will require more studies.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Sree H. Pulugulla, Thomas A. Packard, Nicole L.K. Galloway, Zachary W. Grimmett, Gilad Doitsh, Juraj Adamik, Deborah L. Galson, Warner C. Greene, Philip E. Auron〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Interleukin 1β is a pro-inflammatory cytokine important for both normal immune responses and chronic inflammatory diseases. The regulation of the 31 kDa proIL-1β precursor coded by the 〈em〉IL1B〈/em〉 gene has been extensively studied in myeloid cells, but not in lymphoid-derived CD4 T cells. Surprisingly, we found that some CD4 T cell subsets express higher levels of proIL-1β than unstimulated monocytes, despite relatively low 〈em〉IL1B〈/em〉 mRNA levels. We observed a significant increase in 〈em〉IL1B〈/em〉 transcription and translation in CD4 T cells upon 〈em〉ex vivo〈/em〉 CD3/CD28 activation, and a similar elevation in the CCR5+ effector memory population compared to CCR5− T cells 〈em〉in vivo〈/em〉. The rapid and vigorous increase in 〈em〉IL1B〈/em〉 gene transcription for stimulated monocytes has previously been associated with the presence of Spi-1/PU.1 (Spi1), a myeloid-lineage transcription factor, pre-bound to the promoter. In the case of CD4 T cells, this increase occurred despite the lack of detectable Spi1 at the 〈em〉IL1B〈/em〉 promoter. Additionally, we found altered epigenetic regulation of the 〈em〉IL1B〈/em〉 locus in CD3/CD28–activated CD4 T cells. Unlike monocytes, activated CD4 T cells possess bivalent H3K4me3+/H3K27me3+ nucleosome marks at the 〈em〉IL1B〈/em〉 promoter, reflecting low transcriptional activity. These results support a model in which the 〈em〉IL1B〈/em〉 gene in CD4 T cells is transcribed from a low-activity bivalent promoter independent of Spi1. Accumulated cytoplasmic proIL-1β may ultimately be cleaved to mature 17 kDa bioactive IL-1β, regulating T cell polarization and pathogenic chronic inflammation.〈/p〉〈/div〉 〈/div〉 〈div xml:lang="en"〉 〈h5〉Graphical abstract〈/h5〉 〈div〉〈p〉〈figure〉〈img src="https://ars.els-cdn.com/content/image/1-s2.0-S1043466618303892-ga1.jpg" width="500" alt="Graphical abstract for this article" title=""〉〈/figure〉〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Kexin Hua, Yaqian Li, Hongjian Chen, Jiamin Ni, Dingren Bi, Rui Luo, Hui Jin〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉TRAF family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) serves as hub molecule at the crossroad of multiple signaling pathways of type I interferon (IFN) induction. The importance of TBK1 in innate immunity has been demonstrated in mammalian, however the characterization and function of TBK1 in avian remains largely unknown. In this study, we cloned duck TBK1 (duTBK1) from duck embryo fibroblasts (DEFs) for the first time, which encoded 729 amino acids and had a high amino acid identity with goose and cormorant TBK1s. The duTBK1 showed a diffuse cytoplasmic localization in DEFs and was extensively expressed in all tested tissues. Overexpression of duTBK1 induced IFN-β production through the activation of IRF1 and NF-κB in DEFs. The N-terminal kinase domain and the ubiquitin-like domain in middle of duTBK1 played pivotal roles in IFN-β induction as well as in IRF1 and NF-κB activation. Furthermore, knockdown of duTBK1 by small interfering RNA significantly decreased poly(I:C)- or Sendai virus (SeV)-induced IFN-β expression. In addition, duTBK1 expression dramatically reduced the replication of both duck reovirus (DRV) and duck Tembusu virus (DTMUV) in DEFs. These results suggested that the duTBK1 played a pivotal role in mediating duck antiviral innate immunity.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Shradha Mawatwal, Assirbad Behura, Abtar Mishra, Ramandeep Singh, Rohan Dhiman〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Previously, we reported pivotal role of P2RX7 in augmenting autophagy in THP-1 cells upon Calcimycin treatment by modulating intracellular Calcium regulated ATP production but the role of immune modulators in Calcimycin induced autophagy is not known. In this study, we demonstrate that treatment with Calcimycin in PMA (Phorbol 12-myristate 13-acetate) differentiated THP-1 (dTHP-1) cells significantly induced interleukin (IL)〈em〉-〈/em〉12 mRNA expression and its release. IL-12 receptor (IL-12Rβ1 and IL-12Rβ2) was also significantly expressed on the cell surface in dTHP-1 cells upon Calcimycin treatment. We report that small molecule or siRNA based P2RX7 inhibition abrogated IL-12 release upon Calcimycin treatment. P2RX7 inhibition also resulted in reduced Jun N-terminal kinase (JNK) activation, IκBα phosphorylation, p65 translocation and NF-κB expression. Further, inhibition of NF-κB activation or IL-12-IL-12R interaction led to down-regulation of the expression of autophagy related markers such as Beclin-1, autophagy-related gene (Atg) 3, Atg 7 and impairment of microtubule-associated protein 1A/1B-light chain 3-I (LC3-I) to LC3-II conversion. Finally, blocking of autophagy led to significant growth of intracellular mycobacteria in Calcimycin treated macrophages. Overall, these results reveal that interaction of Calcimycin with P2RX7 modulates intracellular JNK-NF-κB signaling pathway. This modulation results in IL-12 release that restricts the mycobacterial growth in THP-1 macrophages.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Vanessa Fernandes Rodrigues, Márcia Paulliny Soares Bahia, Núbia Rangel Cândido, João Marcelo Peixoto Moreira, Vinicius Gustavo Oliveira, Emília Souza Araújo, Jailza Lima Rodrigues Oliveira, Michelle de Carvalho Rezende, Ary Correa, Deborah Negrão-Corrêa〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Helminth infection can reduce the severity of inflammatory bowel disease. However, the modulatory mechanisms elicited by helminth infection are not yet fully understood and vary depending on the experimental model. Herein we evaluated the effect of acute infection of BALB/c mice with Strongyloides venezuelensis on the clinical course of ulcerative colitis induced by Dextran Sulfate Sodium (DSS) treatment of these animals. For the experiments, 〈em〉S. venezuelensis〈/em〉-infected BALB/c mice were treated orally with 4% DSS solution for seven days. As controls, we used untreated 〈em〉S. venezuelensis〈/em〉 infected, DSS-treated uninfected, and untreated/uninfected BALB/c mice. During DSS treatment, mice from the different groups were compared with regards to the clinical signs related to the severity of colitis and intestinal inflammation. Mice acutely infected with S. venezulensis and treated with DSS had reduced clinical score, shortening of the colon, and tissue inflammation. Moreover, DSS-treated and infected mice showed reduced IL-4, INF-γ, and IL-17 levels and increase of IL-10 production in the colon and/or in the supernatant of mesenteric lymph nodes cell cultures that resulted in lower eosinophil peroxidase and myeloperoxidase activity in colon homogenates, when compared with DSS-treated uninfected mice. DSS-treated infected mice also preserved the intestine architecture and had normal differentiation of goblet cells and mucus production in the colon mucosa. In conclusion, the data indicate that the clinical improvement reported in DSS-treated infected mice was accompanied by the lower production of Th1/Th2/Th17 pro-inflammatory cytokines, stimulation of IL-10, and induction of mucosal repair mechanisms.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Liuqing Wang, Yueying Wang, Liping Xia, Hui Shen, Jing Lu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Objective〈/h6〉 〈p〉To detect the expression of IL-37 and its receptors IL-18Rα and IL-1R8 in CD4〈sup〉+〈/sup〉 T cells and total lymphocytes in rheumatoid arthritis (RA) patients and the relationship between autoantibodies and disease activity. To investigate the mechanism of IL-37 and its receptors involved in the pathogenesis of RA. To evaluate the effects of different concentrations of rhIL-37 on peripheral blood mononuclear cells (PBMCs) in RA patients with TNF-α, and IL-6.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉The expression of IL-37 and its receptor IL-18Rα and IL-1R8 in peripheral blood CD4〈sup〉+〈/sup〉 T cells and total lymphocytes in RA patients and healthy controls were measured by flow cytometry. The levels of TNF-α and IL-6 in the supernatant were measured by ELISA after rhIL-37 stimulation with PBMCs.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉The expression of IL-37 and IL-18Rα in the total lymphocytes, especially in CD4〈sup〉+〈/sup〉 T cells in RA patients, was significantly higher than in the healthy control group. There was a positive correlation between the frequency of IL-37- or IL-18Rα-positive CD4〈sup〉+〈/sup〉 T cells and ESR, CRP, and DAS28 values. Additionally, rhIL-37 significantly down-regulated TNF-α and IL-6 production in RA patients’ PBMCs.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉IL-37 plays an important role in the regulation of inflammation in RA. IL-37 and its receptors may play an immunoregulatory role in the activation of lymphocytes, especially CD4〈sup〉+〈/sup〉 T cells, in RA patients. IL-37 may represent a therapeutic target for rheumatoid arthritis.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Joseph T. Costello, Rebecca A. Rendell, Matthew Furber, Heather C. Massey, Michael J. Tipton, John S. Young, Jo Corbett〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study examined the acute and chronic effects of euhydrated and hypohydrated heat exposure, on biomarkers of stress and inflammation. Eight trained males [mean (SD) age: 21 (3) y; mass: 77.30 (4.88) kg; V̇O〈sub〉2max〈/sub〉: 56.9 (7.2) mL kg〈sup〉−1〈/sup〉 min〈sup〉−1〈/sup〉] undertook two heat acclimation programmes (balanced cross-over design), once drinking to maintain euhydration and once with restricted fluid-intake (permissive dehydration). Days 1, 6, and 11 were 60 min euhydrated exercise-heat stress tests (40 °C; 50% RH, 35% peak power output), days 2–5 and 7–10 were 90 min, isothermal-strain (target rectal temperature: 38.5 °C) exercise-heat sessions. Plasma was obtained pre- and post- exercise on day 1, 2, and 11 and analysed for cortisol, interleukin-6 (IL-6), and C-reactive protein (CRP). Cortisol and CRP were also assessed on day 6. IL-6 was elevated following the initial (acute) 90 min isothermal heat strain exercise-heat exposure (day 2) with permissive dehydration ((pre exercise: 1.0 pg mL〈sup〉−1〈/sup〉 [0.9], post-exercise: 1.8 pg mL〈sup〉−1〈/sup〉 [1.0], P = .032) and when euhydrated (pre-exercise: 1.0 pg mL〈sup〉−1〈/sup〉 [1.4], post-exercise: 1.6 pg mL〈sup〉−1〈/sup〉 [2.1], P = .048). Plasma cortisol levels were also elevated but only during permissive dehydration (P = .032). Body mass loss was strongly correlated with Δcortisol (r = −0.688, P = .003). Although there was a trend for post-exercise cortisol to be decreased following both heat acclimation programmes (chronic effects), there were no within or between intervention differences in IL-6 or CRP. In conclusion, acute exercise in the heat increased IL-6 and cortisol only when fluid-intake is restricted. There were no chronic effects of either intervention on biomarkers of inflammation as evidenced by IL-6 and CRP returning to basal level at the end of heat acclimation.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Di Che, Lei Pi, Yufen Xu, LanYan Fu, Huazhong Zhou, Zhouping Wang, Ping Huang, Li Zhang, Xiaoqiong Gu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Kawasaki disease is a multi-system vasculitis and a primary cause of acquired heart disease among children. Genetic factors may increase susceptibility to Kawasaki disease. 〈em〉TBXA2R〈/em〉 is a G-protein-coupled receptor that participates in tissue inflammation and is associated with susceptibility to several diseases, but its relevance in Kawasaki disease is unclear. We genotyped 〈em〉TBXA2R〈/em〉 (rs1131882 and rs4523) in 694 Kawasaki disease cases and 657 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the intensity of the associations. We found a significantly decreased risk of Kawasaki disease associated with 〈em〉TBXA2R〈/em〉 rs4523 G variant genotypes (AG vs AA: adjusted OR = 0.788, 95%CI = 0.626–0.993; GG vs AA: adjusted OR = 0.459, 95%CI = 0.258–0.815; AG/GG vs AA: adjusted OR = 0.744, 95%CI = 0.595–0.929; GG vs AG/AA: adjusted OR = 0.497, 95% CI = 0.281–0.879). In the combined analysis of the two single-nucleotide polymorphisms (SNPs), we found that individuals with two unfavorable genotypes exhibited decreased risk for Kawasaki disease (adjusted OR = 0.754, 95%CI = 0.577–0.985) compared with those who did not have or one unfavorable genotypes. This cumulative effect on protection is effect-genotype dose-dependent (p〈sub〉trend〈/sub〉 = 0.022). Moreover, the combined analysis indicated that the two unfavorable genotypes were associated with a decreased risk of Kawasaki disease in children 12–60 months of age, females and the subgroup with non-coronary artery lesion (NCAL) formation compared with those who did not have or one unfavorable genotypes. In conclusion, the 〈em〉TBXA2R〈/em〉 rs4523 G allele may contribute to protection against Kawasaki disease and decreased risk of coronary artery aneurysm complications in a southern Chinese population.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Naoto Sakumura, Masaki Shimizu, Mao Mizuta, Natsumi Inoue, Yasuo Nakagishi, Akihiro Yachie〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉This study aims to investigate the clinical significance of serum soluble CD163 (sCD163) levels as a predictor of the disease activity of systemic juvenile idiopathic arthritis (s-JIA). In this study, we examined 63 patients with s-JIA, four with Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis (EBV-HLH), and seven with Kawasaki disease (KD), along with 14 healthy controls. We quantified serum cytokine levels (sCD163, neopterin, IL-18, IL-6) by enzyme-linked immunosorbent assay and compared the results with the clinical features of s-JIA. Serum sCD163 levels were significantly elevated in patients with s-JIA associated macrophage activation syndrome (MAS) and EBV-HLH compared to those in patients with acute-phase s-JIA and KD. In addition, serum sCD163 levels profoundly increased with the progress of MAS and correlated positively with the disease activity of s-JIA, even in patients receiving tocilizumab. Furthermore, serum sCD163 levels significantly decreased in the inactive phase compared to those in the active phase and normalized in remission. The correlation between macrophage activation and serum sCD163 levels might be a unique indicator of the disease activity and a potential diagnostic laboratory criterion for clinical remission in patients with s-JIA, including those receiving tocilizumab.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Erfan Ayubi, Saeid Safiri〈/p〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Alan Leviton, Robert M. Joseph, Elizabeth N. Allred, Raina N. Fichorova, T. Michael O'Shea, Karl K.C. Kuban, Olaf Dammann〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Interleukin (IL)-4 and IL-10 are viewed mainly as anti-inflammatory cytokines. Yet, high concentrations have also been associated with inflammation-related diseases in newborns.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉We measured the concentrations of IL-4 and IL-10, as well as IL-8 and ICAM-1 in blood specimens collected on postnatal day 21 (N = 555), day 28 (N = 521), and both days 21 and 28 (N = 449) from children born extremely preterm (EP) (〈28 weeks gestation) who at age 10 years had a DAS-II IQ Z-score 〉 −2 (which approximates a score of 〉70) and the following assessments, CCC-2, and CSI-4, DAS-II, NEPSY-II, OWLS-II, SCQ, and WIAT-III. Selected children also were assessed with the ADI-R and the ADOS-2. We modeled the risk of low scores or dysfunctions associated with top quartile concentrations of IL-4 and IL-10 on each day and on both days.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉The risks of low scores on the Animal Sorting and Arrows components of the NEPSY-II, both components of the OWLS-II, and the PseudoWord and Spelling components of the WIAT-III were heightened among children who had top quartile concentrations of IL-4 on postnatal days 21 and 28. Children who had high concentrations of IL-10 on days 21 and 28, individually and collectively, were at increased risk of low scores on the WIAT-III Spelling component. High concentrations of IL-4 on day 28 were associated with autism spectrum disorder (ASD). High concentrations of IL-10 on day 28 were also associated with a doubling of ASD risk, but this did not achieve statistical significance. Top quartile concentrations of IL-4 and IL10 on both days were not associated with increased risk of social, language, or behavioral dysfunctions.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉Among children born EP, those who had top quartile concentrations of IL-4 and/or IL-10 on postnatal days 21 and/or 28 were more likely than their peers to have low scores on components of the NEPSY-II, OWLS-II, and WIAT-III assessments, as well as identification as having an ASD.〈/p〉 〈p〉What is known:〈/p〉 〈dl〉 〈dt〉•〈/dt〉 〈dd〉〈p〉IL-4 and IL-10 are viewed as predominantly anti-inflammatory proteins.〈/p〉〈/dd〉 〈dt〉•〈/dt〉 〈dd〉〈p〉Less commonly, high concentrations of IL-4 and IL-10 have been associated with adverse health outcomes.〈/p〉〈/dd〉 〈/dl〉 〈p〉What is not known:〈/p〉 〈dl〉 〈dt〉•〈/dt〉 〈dd〉〈p〉We do not know to what extent elevated concentrations of IL-4 and IL-10 during the third and fourth postnatal weeks are associated with increased risk of neurocognitive, behavioral, language, and social dysfunctions among children born very preterm.〈/p〉〈/dd〉 〈/dl〉 〈p〉What this study adds:〈/p〉 〈dl〉 〈dt〉•〈/dt〉 〈dd〉〈p〉Children born very preterm who have elevated concentrations of IL-4, but not IL-10, on both postnatal days 21 and/or 28 are at increased risk of low scores on assessments of processing speed, visuospatial skills, listening comprehension, oral expression, and reading and spelling achievement.〈/p〉〈/dd〉 〈/dl〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: Available online 6 October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine〈/p〉 〈p〉Author(s): Rosario García-Rocha, Alberto Monroy-García, Jorge Hernández-Montes, Benny Weiss-Steider, Vianey Gutiérrez-Serrano, María del Carmen Fuentes-Castañeda, Luis Roberto Ávila-Ibarra, Christian Azucena Don-López, Daniela Berenice Torres-Pineda, María de Lourdes Mora-García〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉In cancer, the adenosinergic pathway participates in the generation of an immunosuppressive microenvironment and in the promotion of tumor growth through the generation of adenosine (Ado). The present study analyzed the participation of Ado, generated through the functional activity of the cervical cancer (CeCa) pathway in CeCa cells, to induce the expression and secretion of TGF-β1, as well as the participation of this factor to maintain CD73 expression. Ado concentrations greater than 10 μM were necessary to induce an increase of over 50% in the production and expression of TGF-β1 in CeCa tumor cells. Blockade of A2AR and A2BR with the specific antagonists, ZM241385 and MRS1754, respectively, strongly reversed the production of TGF-β1. TGF-β1 produced by CeCa cells was necessary to maintain CD73 expression because the addition of anti-TGF-β neutralizing antibodies or the inhibition of TGF-βRI strongly reversed the expression of CD73 in the CeCa cells. These results suggested a feedback loop in CeCa cells that favors immunosuppressive activity through the production of TGF-β1 and Ado as well as the autocrine activity of TGF–β1 and expression of CD73.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Claudia Terraza, Ricardo Fuentes, Karina Pino-Lagos〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The immune regulatory properties of IL-33 have indicated that this cytokine has the capacity to target several immune cells under a variety of immunological responses, including overt inflammation and tolerance. Due to its versatile mechanistics, we sought to investigate the role of IL-33 on mesenchymal stem cells (MSC), a population of cells with recognizable modulatory functions. Our data indicates that IL-33 does not affect the expression of classical MSC markers such as CD29, CD44 and CD73, or the lack of CD45, CD11b and CD117. Also, we found that IL-33 greatly induces iNOS expression and stimulates the secretion of TGF-β and IL-6. Next, we decided to test IFN-γ/IL-33-treated MSC using a skin transplantation model. Our data indicate that allogeneic skin-grafted animals treated with IFN-γ/IL-33-modulated MSC reject as controls. Complementing this finding, we observed that 〈em〉ex vivo〈/em〉 re-stimulated draining lymph nodes (dLN) cells from these mice secrete lower amounts of IFN-γ and a slightly higher amount of IL-17. Beside a reduction in CD4+ and CD8+ T cells number, we preliminarily found an increment in the frequencies of CD4+Foxp3+IL-17+ T cells. Altogether, our data propose that IL-33 and IFN-γ modulate MSC phenotype and function, most likely targeting Th1/Th17 axis.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Bin Pan, Fan Xia, Yujing Wu, Fan Zhang, Zhenzhen Lu, Ruixue Fu, Longmei Shang, Lingling Li, Zengtian Sun, Lingyu Zeng, Kailin Xu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Acute graft-versus-host disease (aGVHD) remains a major challenging complication of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). CD4〈sup〉+〈/sup〉 effector T cells and their related cytokines mediate pathogenesis of aGVHD, in which donor-T-cell derived interleukin-22 (IL-22) was recently indicated to play a role. The role of recipient-derived IL-22 in aGVHD remains to be elucidated. By applying IL-22 knock out (IL-22KO) mice as recipients of allotransplant, we found recipient derived IL-22 alleviated aGVHD and improved survival of allotransplant recipients. Knock out of IL-22 in recipient increased levels of T-helper (Th1) 1 cells but decreased levels of regulatory T cells (Tregs) in target tissues of aGVHD. Levels of IL-22 increased in aGVHD mice. Recipient antigen presenting cells (APCs) are important sources of IL-22. IL-22 reduced activation of APCs 〈em〉in vitro〈/em〉. Defect of IL-22 in APCs resulted in increased polarization of Th1 cells but decreased level of Tregs in an 〈em〉in vitro〈/em〉 co-culture system. Our data highlight an immunoregulatory function of recipient-derived IL-22 in aGVHD.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Adam Molyvdas, Urania Georgopoulou, Nikolaos Lazaridis, Prodromos Hytiroglou, Alexios Dimitriadis, Pelagia Foka, Themistoklis Vassiliadis, Georgia Loli, Athanasios Phillipidis, Pantelis Zebekakis, Anastasios E. Germenis, Matthaios Speletas, Georgios Germanidis〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background and aims〈/h6〉 〈p〉Chronic viral hepatitis is a prevalent disease with major health implications. Its underlying pathophysiological mechanisms are not fully understood. IL-1β and the NLRP3 inflammasome involvement has been suggested in recent years, from 〈em〉in vitro〈/em〉 data and data from peripheral blood samples. Therefore, we investigated IL-1β and the NLRP3 inflammasome in liver tissues in an effort to clarify their role in the pathophysiology of chronic viral hepatitis.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉We studied liver biopsies from patients with a new diagnosis of either chronic hepatitis B (CHB) and chronic hepatitis C (CHC) or patients with chronic hepatitis B in remission (CHB-rem). The biopsies were separated in two parts. The first part was sent to histology to determine the grade of inflammation and fibrosis. From the second part, RNA was extracted and converted to cDNA used in semi-quantitative Real-Time PCR to measure the levels of 〈em〉IL1B〈/em〉, 〈em〉CASP1〈/em〉, 〈em〉NLRP3〈/em〉, 〈em〉ASC〈/em〉 and 〈em〉IL1RA〈/em〉. The cell lines used in the 〈em〉in vitro〈/em〉 experiments were Huh7.5, LX2 and THP-1 in variety of combinations of monocultures, co-cultures and triple cultures with one of the cell lines infected with the JFH-1 HCV clone. From the cell cultures RNA was extracted and converted to cDNA. For cell lines, we focused in the expression of 〈em〉IL1B〈/em〉 and 〈em〉NLRP3〈/em〉.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉The expression of 〈em〉IL1B〈/em〉, 〈em〉CASP1〈/em〉 and 〈em〉NLRP3〈/em〉 were found significantly different between our groups (p = 0.001, p = 0.001 and p = 0.038, respectively). CHB patients displayed significantly higher 〈em〉IL1B〈/em〉 and 〈em〉CASP1〈/em〉 mRNA levels compared to both CHB-rem and CHC patients. 〈em〉IL1B〈/em〉 expression significantly correlates with liver biochemical data in CHB patients (AST: p = 0.006, r = 0.457; ALT p = 0.002, r = 0.497). Finally, mRNA levels of 〈em〉IL1B〈/em〉 in CHB patients significantly correlate with the degree of inflammation (p = 0.016) but not the stage of fibrosis (p = 0.362). Interestingly, the relative expression of 〈em〉IL1B〈/em〉 in triple culture experiments 〈em〉in vitro〈/em〉 was below of 1.5-fold, suggesting no activation of 〈em〉IL1B.〈/em〉 Moreover, no activation of 〈em〉NLRP3〈/em〉 was demonstrated in all investigated 〈em〉in vitro〈/em〉 conditions.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉IL-1β might play an important role in the pathogenesis of chronic hepatic inflammation from HBV, but not from HCV.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Malgorzata Krzystek-Korpacka, Marek Zawadzki, Bartosz Kapturkiewicz, Paulina Lewandowska, Iwona Bednarz-Misa, Sabina Gorska, Wojciech Witkiewicz, Andrzej Gamian〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉Colorectal cancers (CRCs) are treated as one entity but are in fact a heterogeneous group of diseases. If not addressed, subsite-associated variability may interfere with mechanism-targeted therapies and accuracy of potential CRC biomarkers. Little is known about the contribution of systemic inflammatory and immune mediators to subsite heterogeneity in CRC. Our purpose was to compare the profiles of key cytokines between right and left colonic and rectal CRCs. Using Luminex xMAP® technology, serum concentrations of eotaxin, IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17, IFNγ, IP-10, FGF-2, G-CSF, GM-CSF, MCP-1, MIP-1α and β, PDGF-BB, RANTES, TNFα, and VEGF-A were determined in 104 CRC patients. We found the concentrations of IL-12(p70), IL-10, IL-1ra, IL-4, IL-6, IL-7, IL-8, G-CSF and TNFα to be significantly higher in right-sided and GM-CSF in left-sided than rectal CRCs. The concentrations of IFNγ and MIP-1α were significantly higher in right-sided CRCs as compared to cancers of other locations combined. In turn, MIP-1β was higher in rectal CRCs as compared to colon cancers. Taken together, our results show subsite heterogeneity of CRC cancers in terms of systemic inflammatory and immune responses that ought to be taken into account when attempting immunotherapy or developing biomarkers. Additionally, more pronounced T〈sub〉H〈/sub〉2 response accompanied by T〈sub〉H〈/sub〉1 immunity and more prominent tumor-promoting inflammation in CRC patients with primary tumors originating from right-sided colon may constitute a molecular background of unfavorable prognosis associated with this location.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Kamakshi Prudhula Devalraju, Venkata Sanjeev Kumar Neela, Ramulu Gaddam, Arunabala Chaudhury, Abhinav Van, Siva Sai Krovvidi, Ramakrishna Vankayalapati, Vijaya Lakshmi Valluri〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉HIV infection markedly increases the likelihood of latent tuberculosis infection progressing to active TB. Information on expression of TLR-2, myeloid differentiation factor (MyD88), IL-1R- associated kinase-4 (IRAK4) and nuclear factor kappa B (NF-kB) in HIV+LTBI+ and HIV+ patients with active TB disease is limited. We found significantly higher percentages of CD14+TLR2+ cells in PBMCs of HIV+LTBI+ patients compared to HIV−LTBI+ individuals. γ-irradiated Mtb was unable to induce MyD88, IRAK4 expression and IL-1β, MCP-1, IP-10 production in HIV+LTBI+ patients. Pleural fluids from HIV+TB+ patients had low IL-1β, MCP-1, IP-10 and high IL-10, TNF-α production. γ-irradiated Mtb stimulated CD14+ cells from HIV+TB+ patients had low IL-1β, MCP-1, IP-10 production and MyD88, IRAK4 and similar NF-kB expression compared to those from of HIV−TB+ patients. Our results suggest defective MyD88, IRAK4 but not NF-kB inhibit IL-1β, MCP-1 and IP-10 production by CD14+ cells of HIV+ individuals with LTBI and active TB disease in peripheral blood and at the site of disease.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): N. Kouvas, C. Kontogiannis, G. Georgiopoulos, M. Spartalis, D.I. Tsilimigras, E. Spartalis, A. Kapelouzou, M. Kosmopoulos, S. Chatzidou〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The network of cytokines consists one of the most extensively studied signaling systems of human body. Cytokines appear to modulate pathogenesis and progress of many different diseases in the human body, particularly in regards to cardiovascular system. However, their effects on the electrical system of the heart has been neglected. Over the past decade, attemps to understand this relationship led to the uncovering of the direct and indirect effects of cytokines on action potential propagation and cell depolarization. This relationship has been depicted in clinical practice as serum levels of cytokines are increasingly associated with prevalence of ventricular arrhythmias either isolated or secondary to either a heart condition or a systemic auto-immune disease. Thus, they present an appealing potential as a biomarker for prediction of arrhythmia generation, as well as the ourtcome of electrophysiological interventions.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Jude PJ Savarraj, Mary F McGuire, Kaushik Parsha, Georgene Hergenroeder, Suhas Bajgur, Sungho Ahn, Liang Zhu, Elena Espino, Tiffany Chang, Spiros Blackburn, Dong H Kim, Pramod Dash, Huimahn A Choi〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Unregulated inflammatory and thrombotic responses have been proposed to be important causes of early brain injury and worse clinical outcomes after subarachnoid hemorrhage (SAH).〈/p〉 〈/div〉 〈div〉 〈h6〉Objective〈/h6〉 〈p〉We hypothesize that SAH is characterized by an increased inflammatory and thrombotic state and disruption of associations between these states.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉This is a retrospective cohort study of 60 patients with SAH. 23 patients with unruptured aneurysms (UA) and 77 patients with traumatic brain injury (TBI) were chosen as controls. Plasma cytokine levels were measured using a 41-plex human immunoassay kit, and cytokine patterns associated with SAH, UA and TBI were identified using statistical and informatics methods.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉SAH was characterized by an increase in several cytokines and chemokines, platelet-derived factors, and growth factors. Cluster analysis identified several cytokine clusters common in SAH, UA and TBI groups – generally grouped as platelet-derived, vascular and pro-inflammatory clusters. In the UA group, the platelet-derived cluster had an inverse relationship with the inflammatory cluster which was absent in SAH. Additionally, a cluster comprising of growth and colony stimulating factors was unique to SAH.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉A cluster of cytokines involved in growth and colony stimulation was unique to SAH. Negative associations between the thrombotic and inflammatory molecules were observed in UA but not in SAH. Further studies to examine the pathophysiology behind the cluster unique to SAH and the associations between the thrombotic and inflammatory cytokines are required.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Katarzyna Mizia-Stec, Joanna Wieczorek, Mateusz Polak, Maciej T. Wybraniec, Iwona Woźniak-Skowerska, Andrzej Hoffmann, Seweryn Nowak, Maria Wikarek, Anna Wnuk-Wojnar, Jerzy Chudek, Andrzej Więcek〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Aims〈/h6〉 〈p〉The proarrhythmic effect of fibroblast growth factor 23 (FGF23) was observed in patients with end stage kidney disease (ESKD). However, there is no data on the role of FGF23 and soluble Klotho (sKlotho) in the pathogenesis of atrial fibrillation (AF) beyond ESKD. The aim of the study was to assess the peripheral vein and left atrial (LA) serum levels of FGF23 and sKlotho along with calcium-phosphates parameters in patients with AF undergoing percutaneous radiofrequency pulmonary vein isolation (PVI).〈/p〉 〈/div〉 〈div〉 〈h6〉Methods and results〈/h6〉 〈p〉Sixty-nine consecutive patients (mean age: 55.8 ± 9.7 years, F/M: 26/43, CHA2DS2-Vasc: 1.7 ± 1.1) with paroxysmal/persistent AF undergoing PVI were included into the study. Blood samples were taken during PVI – baseline from the peripheral vein, then from the LA immediately after a septal puncture.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉There were significant differences in the concentrations of peripheral and LA serum sKlotho, intact FGF23 (iFGF23), calcium and phosphates; peripheral FGF23, calcium and phosphates levels were significantly higher, and sKlotho levels were significantly lower than the LA concentrations. Serum sKlotho levels correlated with the CHADS2-VASc score (r = 0.254, p = 0.034) and glucose level (r = 0.300, p = 0.005). Serum sKlotho gradient (LA – peripheral vein) correlated with the baseline AF burden in the Holter monitoring (r = −0.389, p = 0.003). PVI efficacy was confirmed in 52 (75%) patients. There was a significant difference in the iFGF23 gradient between patients with AF and without AF (80.3 vs. −47.6 pg/ml, p = 0.009) in the six-month follow-up. A receiver operating characteristic (ROC) analysis revealed that an iFGF23 gradient 〉28.7 pg/ml (AUC = 0.742, p = 0.002) was a predictor for AF recurrence.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉There is a gradient between the LA and peripheral vein in the markers of calcium-phosphate metabolism in patients undergoing PVI. Lower sKlotho and higher iFGF23 serum levels are associated with episodes of AF. Serum iFGF23 gradient is a potent predictor for the recurrence of AF.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Vanessa Aust, Eugenia Kress, Stephanie Abraham, Nicole Schröder, Markus Kipp, Matthias B. Stope, Thomas Pufe, Simone C. Tauber, Lars-Ove Brandenburg〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈p〉Pneumococcal meningitis, caused by 〈em〉Streptococcus pneumoniae〈/em〉, is the most common type of bacterial meningitis. The clinical management of this disease has been challenged by the emergence of multidrug-resistant 〈em〉Streptococcus pneumoniae〈/em〉, requiring the urgent development of new therapeutic alternatives. Over the course of bacterial meningitis, pathogen invasion is accompanied by a massive recruitment of peripheral immune cells, especially neutrophil granulocytes, which are recruited under the coordination of several cytokines and chemokines. Here, we used chemokine (C-C motif) ligand 3 (〈em〉Ccl3〈/em〉)-deficient mice to investigate the functional role of CCL3 in a mouse model of pneumococcal meningitis.〈/p〉 〈p〉Following intrathecal infection with 〈em〉Streptococcus pneumoniae Ccl3〈/em〉-deficient mice presented a significantly shorter survival and higher bacterial load than wildtype mice, paralleled by an ameliorated infiltration of neutrophil granulocytes into the CNS. Blood sample analysis revealed that infected 〈em〉Ccl3〈/em〉-deficient mice showed a significant decrease in erythrocytes, hemoglobin and hematocrit as well as in the number of banded neutrophils. Moreover, infected 〈em〉Ccl3〈/em〉-deficient mice showed an altered cytokine expression profile. Glial cell activation remained unchanged in both genotypes.〈/p〉 〈p〉In summary, this study demonstrates that CCL3 is beneficial in 〈em〉Streptococcus pneumoniae〈/em〉-induced meningitis. Pharmacological modulation of the CCL3 pathways might, therefore, represent a future therapeutic option to manage 〈em〉Streptococcus pneumoniae〈/em〉 meningitis.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Ken-ichiro Sasaki, Yuta Ishizaki, Motoki Sasaki, Takaharu Nakayoshi, Masanori Ohtsuka, Hiroo Matsuse, Naoto Shiba, Takafumi Ueno, Yoshihiro Fukumoto〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉The hybrid training system (HTS) is a special and compact system for effective skeletal muscle training by a combined application of volitional and electrical muscle contraction. Lower limbs’ muscle training using HTS has been reported to increase not only muscle strength but also plasma interleukin-6 levels; however, little is known in other cytokines. In this study, we measured 52 cytokines and creatine phosphokinase-MM in the serum of 16 healthy men before and after lower limbs’ muscle training by the knee flexion and extension using HTS. Skeletal muscle volume-corrected serum concentrations of cutaneous T-cell-attracting chemokine, erythropoietin, and tumor necrosis factor-related apoptosis-inducing ligand increased immediately after the training. These increased cytokines have been reported to play important roles in wound healing, neuroprotection, and cardiovascular protection.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Bing Wan, Wu-jian Xu, Ping Zhan, Jia-jia Jin, Guang-min Xi, Mei-zi Chen, Yang-bo Hu, Su-hua Zhu, Hong-bing Liu, Xiao-xia Wang, Xiu-wei Zhang, Tang-Feng Lv, Yong Song〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Objective〈/h6〉 〈p〉We investigated the effect of topotecan on injury and inflammation in a model of ventilator-induced lung injury (VILI).〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Acute lung injury (ALI) was induced in mice by high-tidal volume ventilation, and the mice were then treated with topotecan or PBS. Lung tissue and bronchoalveolar lavage fluid were collected to assess pulmonary vascular leaks, inflammation, and cell apoptosis.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Compared to PBS treatment, topotecan significantly decreased the ALI score, myeloperoxidase (MPO) content, total protein concentration, and presence of inflammatory cells and inflammatory cytokines in bronchoalveolar lavage fluid. Topotecan also reduced caspase-3 activation and type Ⅱ alveolar epithelial cell apoptosis. Moreover, topotecan inhibited NF-κB expression and activation in the VILI model.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉Topotecan alleviates acute lung injury in the model of VILI through the inhibition of the NF-κB pathway.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: November 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 111〈/p〉 〈p〉Author(s): Jia Zhang, Jianbin Bi, Yifan Ren, Zhaoqing Du, Teng Li, Qingshan Li, Mengyun Ke, Jian Dong, Yi Lv, Rongqian Wu〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background & Aims〈/h6〉 〈p〉Gut ischemia reperfusion (I/R) injury is a life-threatening condition. The immune response plays an important role in I/R-induced organ injury. Alpha-galactosylceramide (α-GalCer) is a potent natural killer T (NKT) cell stimulator. Activation of NKT cells by α-GalCer has been shown to reduce I/R-induced injury in the liver and heart. However, whether α-GalCer has any protective effects on gut I/R-induced organ injury remained unknown. The aim of this study was to test the hypothesis that α-GalCer attenuates gut I/R-induced local and remote organ injury through modulating immune responses.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery for 30 min in male adult mice. After removing the clip, α-GalCer (2 µg/mouse) or normal saline containing 0.5% Tween 20 (Vehicle) was administered intraperitoneally. Blood, gut, lung and mesenteric lymph node (MLN) samples were collected 4 h after reperfusion to detect bacterial translocation, tight junction protein, tissue damage, edema, apoptosis, IL-4, IL-10, IFN-γ and TNF-α levels.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉α-GalCer significantly reduced bacterial translocation to the MLN, restored tight junction protein and attenuated gut and lung injury after gut I/R. α-GalCer markedly stimulated the production of IL-4, IL-10 and IFN-γ, but had no obvious effects on TNF-α production in gut I/R mice. Pretreatment with anti-CD1d, IL-4 or IL-10, but not IFN-γ blocking antibodies abolished the protective effects of α-GalCer in gut I/R.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusions〈/h6〉 〈p〉α-GalCer treatment improved gut barrier function and attenuated gut and lung injury after gut I/R. The beneficial effects of α-GalCer in gut I/R were NKT cell dependent and mediated through upregulation of IL-4 and IL-10. Thus, activation of NKT cells by α-GalCer may serve as a novel option in the treatment of gut I/R injury.〈/p〉 〈/div〉 〈/div〉

Description: 〈p〉Publication date: January 2019〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 113〈/p〉 〈p〉Author(s): Jun Ho Yi, Kyung Ju Ryu, Young Hyeh Ko, Won Seog Kim, Seok Jin Kim〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉〈p〉To better predict the outcomes of patients with peripheral T-cell lymphoma (PTCL), we measured the levels of various cytokines in serum samples from patients with PTCL and analyzed their clinical outcomes. We measured 34 cytokines in samples from 121 PTCL patients (55 PTCL-not otherwise specified (NOS), 44 angioimmunoblastic T-cell lymphoma (AITL), and 22 ALK〈sup〉−〈/sup〉 anaplastic large cell lymphoma) at diagnosis. Their impact on clinical outcomes, including overall survival and complete response rate, were analyzed with other clinical variables. The median age of patients was 58 years (range, 20–85 years) and 81 patients (66.9%) were male. The median overall survival among all patients was 56.1 months (95% CI 21.4–90.8) and median progression-free survival was 19.3 months (95% CI 12.3–26.3). Patients with AITL were more likely to express higher levels of serum cytokines, and 7 cytokines showed mean levels that were significantly higher than those in other subtypes. In this subgroup, IL-10 higher than 3.8 pg/mL was associated with adverse outcomes. In patients with ALK〈sup〉−〈/sup〉 anaplastic large cell lymphoma, 9 cytokines showed a prognostic impact, with higher levels of interferon γ, interleukin (IL)-8, IL-10, IL-17, IL-23, IP-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and RANTES negatively affecting clinical outcomes. In PTCL-NOS, patients with elevated levels of interferon γ, IL-7, and IL-23 showed poor outcomes. The current analysis demonstrated different cytokine profiles according to histologic subtype, which revealed the heterogeneity of PTCL. In addition, cytokine levels can be used as prognostic markers and may be useful for therapeutic applications in PTCL patients.〈/p〉〈/div〉 〈/div〉

Description: 〈p〉Publication date: October 2018〈/p〉 〈p〉〈b〉Source:〈/b〉 Cytokine, Volume 110〈/p〉 〈p〉Author(s): Nesrine A Mohamed, Marwa Rushdy, Asmaa S.M. Abdel-Rehim〈/p〉 〈div xml:lang="en"〉 〈h5〉Abstract〈/h5〉 〈div〉 〈h6〉Background〈/h6〉 〈p〉Zinc deficiency may play an important role in the development of atopic asthma.〈/p〉 〈/div〉 〈div〉 〈h6〉The aim of the work〈/h6〉 〈p〉To assess serum zinc levels in adult atopic, non-atopic asthmatic patients, and in healthy controls and to investigate its modulatory effect on production of interferon gamma (IFN-γ) and interleukin-10 (IL-10) by peripheral blood mononuclear cells (PBMCs) in vitro.〈/p〉 〈/div〉 〈div〉 〈h6〉Methods〈/h6〉 〈p〉Sixty asthmatics and 30 apparently healthy volunteers were included in this study. All patients were subjected to history taking, clinical examination, pulmonary function tests, skin prick test (SPT), serum zinc assessment by a colorimetric method as well as serum total IgE measurement by Enzyme-linked immunosorbent assay (ELISA). PBMCs were activated in vitro in the presence and absence of zinc, and then cell culture supernatants were analyzed for IFN-γ and IL-10 by ELISA.〈/p〉 〈/div〉 〈div〉 〈h6〉Results〈/h6〉 〈p〉Serum zinc levels were significantly lower in atopic asthmatics than non-atopic asthmatics and healthy controls. In atopic asthmatics, highly significant correlations were found between zinc levels and total Ig E levels as well as FEV1. In culture, zinc triggers IFN-γ and inhibits IL-10 production by PBMCs, in atopic asthmatics. In non atopic asthmatics and healthy controls, IFN-γ and IL-10 were slightly affected by zinc supplementation in culture.〈/p〉 〈/div〉 〈div〉 〈h6〉Conclusion〈/h6〉 〈p〉Serum zinc levels affect asthma phenotypes. Atopic asthmatics might benefit from zinc supplements.〈/p〉 〈/div〉 〈/div〉