NDLI: Reduced Paneth cell α-defensins in ileal Crohn's disease

Content Provider	PubMed Central
Author	Wehkamp, Jan Salzman, Nita H. Porter, Edith Nuding, Sabine Michael, Weichenthal Petras, Robert E. Shen, Bo Elke, Schaeffeler Schwab, Matthias Linzmeier, Rose Feathers, Ryan W. Chu, Hiutung Lima, Heriberto Klaus, Fellermann Ganz, Tomas Stange, Eduard F. Bevins, Charles L.
Copyright Year	2005
Abstract	The pathogenesis of Crohn′s disease (CD), an idiopathic inflammatory bowel disease, is attributed, in part, to intestinal bacteria that may initiate and perpetuate mucosal inflammation in genetically susceptible individuals. Paneth cells (PC) are the major source of antimicrobial peptides in the small intestine, including human α-defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC α-defensins compromises mucosal host defenses and predisposes patients to CD of the ileum. We report that patients with CD of the ileum have reduced antibacterial activity in their intestinal mucosal extracts. These specimens also showed decreased expression of PC α-defensins, whereas the expression of eight other PC products either remained unchanged or increased when compared with controls. The specific decrease of α-defensins was independent of the degree of inflammation in the specimens and was not observed in either CD of the colon, ulcerative colitis, or pouchitis. The functional consequence of α-defensin expression levels was examined by using a transgenic mouse model, where we found changes in HD5 expression levels, comparable to those observed in CD, had a pronounced impact on the luminal microbiota. Thus, the specific deficiency of PC defensins that characterizes ileal CD may compromise innate immune defenses of the ileal mucosa and initiate and/or perpetuate this disease.
Related Links	http://dx.doi.org/10.1073/pnas.0505256102
Starting Page	18129
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	50
Volume Number	102
Language	English
Publisher	National Academy of Sciences
Publisher Date	2005-12-13
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Reduced Paneth cell alpha-defensins in ileal Crohn's disease

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