Aryl hydrocarbon receptor activation ameliorates colitis via transcriptional regulation of -defensin1

Abstract Ulcerative colitis (UC), a chronic inflammatory disease of the colon and rectum accounts for 1.5 million individuals, with an annual incidence of 15 per 100,000 individuals. The etiology of colitis includes host, genetic, environmental, and microbiological factors. The intestinal epithelium can produce antimicrobial molecules for epithelial protection from commensal microorganisms. Aryl hydrocarbon receptor (AhR) plays an important role as an environmental sensor and a regulator of the immune response. Indeed, studies have shown that the expression of AhR was correlated with the expression of a-defensins in inflammatory bowel disease patients. Therefore, the present study was designed to investigate how AhR-ligand activation regulates a-defensin1 in a colitis model. Here, we discovered that in intestinal epithelial cells from colitis mice, dietary Indole-3-carbinol (I3C), a ligand for the AhR, induced AhR and α-defensin1. We also found that AhR-null animals, which are more likely to develop colitis, did not exhibit an increase in α-defensin1 following I3C treatment, indicating that AhR regulates α-defensin1. Similar findings were observed in MC38 cells. Furthermore, the DRE region in the a-defensin1 promoter was involved in the upregulation of a-defensin1 by AhR upon I3C treatment. Collectively, these results provide evidence that AhR activation followed by a-defensin1 production may be a vital prophylactic and therapeutic measure for colitis.