Publication Date:
2005-02-05
Description:
Variants of NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP), increase susceptibility to Crohn's disease (CD). These variants are thought to be defective in activation of nuclear factor kappaB (NF-kappaB) and antibacterial defenses, but CD clinical specimens display elevated NF-kappaB activity. To illuminate the pathophysiological function of NOD2, we introduced such a variant to the mouse Nod2 locus. Mutant mice exhibited elevated NF-kappaB activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1beta (IL-1beta). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maeda, Shin -- Hsu, Li-Chung -- Liu, Hongjun -- Bankston, Laurie A -- Iimura, Mitsutoshi -- Kagnoff, Martin F -- Eckmann, Lars -- Karin, Michael -- AI43477/AI/NIAID NIH HHS/ -- AI56075/AI/NIAID NIH HHS/ -- DK07202/DK/NIDDK NIH HHS/ -- DK35108/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2005 Feb 4;307(5710):734-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0723, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15692052" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylmuramyl-Alanyl-Isoglutamine/immunology
;
Animals
;
Anti-Bacterial Agents/pharmacology
;
Apoptosis
;
Bacteria/immunology
;
Cells, Cultured
;
Colitis/immunology/pathology
;
Colon/*immunology/microbiology
;
Crohn Disease/genetics/*immunology
;
Cytokines/biosynthesis/genetics
;
Dextran Sulfate/pharmacology
;
Interleukin-1/*metabolism
;
Intestinal Mucosa/immunology
;
Intracellular Signaling Peptides and Proteins/*genetics/*physiology
;
Lipopolysaccharides/immunology
;
Macrophage Activation
;
Macrophages/*immunology/metabolism
;
Mice
;
Mutation
;
NF-kappa B/*metabolism
;
Nod2 Signaling Adaptor Protein
;
Peptidoglycan/immunology
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
