Bacterial Regulation of Vitamin D Receptor in Intestinal Epithelial Inflammation

Abstract

Vitamin D deficiency has linked to the development of inflammatory bowel disease. Vitamin D receptor (VDR) is required for all known biologic effects of vitamin D. Previous works focused on the immune response. However, how bacteria regulate VDR expression in intestinal epithelial cells has not been investigated. We investigated the effect of VDR ablation on NF‐κB activation using VDR knockout mouse infected with pathogenic Salmonella or human commensal E. coli. We also investigated the intestinal VDR expression in the germ‐free mice. Mice lacking VDR were in the proinflammatory state and became more susceptible to bacterial infection. Intestinal epithelial cells lacking the VDR exhibit increased NF‐κB activity due to the reduction in IκB levels and the p65 nuclear translocation. VDR expression and distribution were specifically regulated by the bacteria‐induced inflammation. We found that pathogenic bacteria increased VDR expression, whereas commensal bacteria did not change VDR expression in colon epithelial cells. In germ‐free mice, VDR was localized at the top of the crypts of the colon. Bacterial colonization in conventionalized mice induced VDR relocation, and VDR staining was found in the middle and even at the bottom of the crypts. Our data indicate that VDR is involved in suppression of bacteria‐induced intestinal inflammation.