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

Title

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

Creator

Wehkamp J; Salzman N H; Porter E; Nuding S; Weichenthal M; Petras R E; Shen B; Schaeffeler E; Schwab M; Linzmeier R; Feathers R W; Chu H T; Lima H; Fellermann K; Ganz T; Stange E F; Bevins C L

Publisher

Proceedings of the National Academy of Sciences of the United States of America

Date

2005
2005-12

Description

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 alpha-defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC alpha-defensins compromises mucosal host defenses and predisposes patients to CD of the ileum. We report that patients with CID of the ileum have reduced antibacterial activity in their intestinal mucosal extracts. These specimens also showed decreased expression of PC alpha-defensins, whereas the expression of eight other PC products either remained unchanged or increased when compared with controls. The specific decrease of alpha-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 alpha-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.

Subject

bacteria; expression; gene; human intestinal defensin; inflammatory bowel disease; inflammatory bowel disease; innate; innate immunity; intestine; mechanisms; microflora; mutations; peptides; Science & Technology - Other Topics

Format

Journal Article

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

18129-18134

Issue

50

Volume

102

Citation

Wehkamp J; Salzman N H; Porter E; Nuding S; Weichenthal M; Petras R E; Shen B; Schaeffeler E; Schwab M; Linzmeier R; Feathers R W; Chu H T; Lima H; Fellermann K; Ganz T; Stange E F; Bevins C L, “Reduced Paneth cell alpha-defensins in ileal Crohn's disease,” NEOMED Bibliography Database, accessed April 18, 2021, https://neomed.omeka.net/items/show/7552.

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