Other
13 Authors
- Ouellette AJ,
- Hu X,
- Ji Y,
- Lu W,
- Dykstra C,
- Shi J,
- Wang L,
- Liles M,
- Morrison EE,
- van Ginkel FW,
- Aono S,
- Lenz S,
- Elson CO
| First Author | Shi J | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 2 | Pages | 1245-53 |
| PubMed ID | 17617617 | Mgi Jnum | J:149388 |
| Mgi Id | MGI:3848399 | Doi | 10.4049/jimmunol.179.2.1245 |
| Citation | Shi J, et al. (2007) A novel role for defensins in intestinal homeostasis: regulation of IL-1beta secretion. J Immunol 179(2):1245-53 |
| abstractText | 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. |
