Publication Date:
2000-09-01
Description:
Epithelia of the vertebrate intestinal tract characteristically maintain an inflammatory hyporesponsiveness toward the lumenal prokaryotic microflora. We report the identification of enteric organisms (nonvirulent Salmonella strains) whose direct interaction with model human epithelia attenuate synthesis of inflammatory effector molecules elicited by diverse proinflammatory stimuli. This immunosuppressive effect involves inhibition of the inhibitor kappaB/nuclear factor kappaB (IkappaB/NF-kappaB) pathway by blockade of IkappaB-alpha degradation, which prevents subsequent nuclear translocation of active NF-kappaB dimer. Although phosphorylation of IkappaB-alpha occurs, subsequent polyubiquitination necessary for regulated IkappaB-alpha degradation is completely abrogated. These data suggest that prokaryotic determinants could be responsible for the unique tolerance of the gastrointestinal mucosa to proinflammatory stimuli.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neish, A S -- Gewirtz, A T -- Zeng, H -- Young, A N -- Hobert, M E -- Karmali, V -- Rao, A S -- Madara, J L -- DK-35932/DK/NIDDK NIH HHS/ -- DK-47662/DK/NIDDK NIH HHS/ -- DK09800/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 2000 Sep 1;289(5484):1560-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. aneish@emory.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10968793" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Nucleus/metabolism
;
Cysteine Proteinase Inhibitors/pharmacology
;
Cytoskeletal Proteins/metabolism
;
DNA-Binding Proteins/*metabolism
;
Dimerization
;
Humans
;
*I-kappa B Proteins
;
Inflammation Mediators/pharmacology
;
Interleukin-8/genetics/metabolism
;
Intestinal Mucosa/*metabolism/*microbiology
;
Leupeptins/pharmacology
;
Ligases/metabolism
;
NF-kappa B/genetics/*metabolism
;
Phosphorylation
;
Salmonella/pathogenicity/*physiology
;
Salmonella typhimurium/pathogenicity/physiology
;
*Trans-Activators
;
Transcription Factor RelA
;
Tumor Cells, Cultured
;
Tumor Necrosis Factor-alpha/pharmacology
;
Ubiquitin-Protein Ligases
;
Ubiquitins/metabolism
;
beta Catenin
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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