A novel role for defensins in intestinal homeostasis: Regulation of IL-1β secretion

Academic Article


  • Impaired expression of α-defensin antimicrobial peptides and overproduction of the proinflammatory cytokine IL-1β have been associated with inflammatory bowel disease. In this study, we examine the interactions between α-defensins and IL-1β 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 (α-defensins) in the intestine, were more susceptible to dextran sulfate sodium-induced colitis. Furthermore, both baseline and dextran sulfate sodium-induced IL-1β 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-1β production in defensin deficiency in vivo, we evaluated the effect of defensins on IL-1β posttranslational processing and release. It was found that α-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-1β from LPS-activated monocytes, whereas TNF-α expression and release were not affected. Unlike α-defensins, human β-defensins and mouse procryptdins do not have any effect on IL-1β processing and release. Thus, α-defensins may play an important role in intestinal homeostasis by controlling the production of IL-1β. Copyright © 2007 by The American Association of Immunologists, Inc.
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    Digital Object Identifier (doi)

    Author List

  • Shi J; Aono S; Lu W; Ouellette AJ; Hu X; Ji Y; Wang L; Lenz S; Van Ginkel FW; Liles M
  • Start Page

  • 1245
  • End Page

  • 1253
  • Volume

  • 179
  • Issue

  • 2