Open AccessA Novel Role for Defensins in Intestinal Homeostasis: Regulation of IL-1β Secretion
Author(s) -
Jishu Shi,
Shelly Aono,
Wuyuan Lu,
André J. Ouellette,
Xueyou Hu,
Yingbiao Ji,
Lei Wang,
Stephen D. Lenz,
Frederik W. van Ginkel,
Mark R. Liles,
Christine C. Dykstra,
Edward E. Morrison,
Charles O. Elson
Publication year - 2007
Publication title -
the journal of immunology/the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.179.2.1245
Subject(s) - defensin , paneth cell , proinflammatory cytokine , beta defensin , cytokine , secretion , immunology , biology , inflammatory bowel disease , chemistry , inflammation , microbiology and biotechnology , small intestine , endocrinology , medicine , disease , antimicrobial
Impaired expression of alpha-defensin antimicrobial peptides and overproduction of the proinflammatory cytokine IL-1beta have been associated with inflammatory bowel disease. In this study, we examine the interactions between alpha-defensins and IL-1beta and the role of defensin deficiency in the pathogenesis of inflammatory bowel disease. It was found that matrix metalloproteinase-7-deficient (MMP-7(-/-)) mice, which produce procryptdins but not mature cryptdins (alpha-defensins) in the intestine, were more susceptible to dextran sulfate sodium-induced colitis. Furthermore, both baseline and dextran sulfate sodium-induced IL-1beta production in the intestine were significantly up-regulated in MMP-7(-/-) mice compared with that in control C57BL/6 mice. To elucidate the molecular mechanism for the increased IL-1beta production in defensin deficiency in vivo, we evaluated the effect of defensins on IL-1beta posttranslational processing and release. It was found that alpha-defensins, including mouse Paneth cell defensins cryptdin-3 and cryptdin-4, human neutrophil defensin HNP-1, and human Paneth cell defensin HD-5, blocked the release of IL-1beta from LPS-activated monocytes, whereas TNF-alpha expression and release were not affected. Unlike alpha-defensins, human beta-defensins and mouse procryptdins do not have any effect on IL-1beta processing and release. Thus, alpha-defensins may play an important role in intestinal homeostasis by controlling the production of IL-1beta.