Expression of the antimicrobial peptide α-defensin/cryptdins in intestinal crypts decreases at the initial phase of intestinal inflammation in a model of inflammatory bowel disease, IL-10-deficient mice

Abstract

Background: The etiology of inflammatory bowel disease (IBD) is associated with an altered microflora due to a failure of the immune system. This study investigated the expression of the intestinal antimicrobial peptide a-defensin, which plays a pivotal role in the regulation of the intestinal microflora in a representative model of IBD, interleukin (IL)-10-deficient mice. Methods: The expression of α-defensin/cryptdins in IL-10-deficient mice was assessed by real-time polymerase chain reaction (PCR) and acid/urea polyacrylamide gel (AU-PAGE). The alteration of α-defensin/cryptdins expression was compared with the inflammatory grade of mice intestine at various weeks from birth. Results: The weight, length, and inflammation grade of the mouse intestines were assessed at 5, 7, 9, 11, 13, and 15 weeks from birth. While the weight of the large intestine was heavier at 15 weeks after birth in the IL-10-deficient mice than in the control mice, histological inflammation began from 7 weeks after birth. Real-time PCR and AU-PAGE identified a significant decrease in the expression of α-defensin/cryptdins at 7 weeks after birth in the IL-10 knockout mice, thus illustrating the involvement of α-defensin/cryptdins in the etiology of the intestinal inflammation in IBD. This study also identified the expression of α-defensin/cryptdins to be inversely proportional to age until 11 weeks, suggesting a relationship between the formation of the intestinal microflora and a reduction in the expression of α-defensin/cryptdins. Conclusions: The altered expression of antimicrobial peptide α-defensin may cause the onset of intestinal inflammation due to a failure to regulate intestinal microflora. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.