Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-κB target gene expression

• DOI: 10.1152/ajpgi.00528.2006
• Publication Date: 2006-12-14T20:30:26Z
• Authors: Yatrik M. Shah; Xiaochao Ma; Keiichirou Morimura; Insook Kim; Frank J. Gonzalez
• Keywords: Pregnane X receptor; Proinflammatory cytokine

Pregnane X receptor (PXR) expression was shown to be protective in inflammatory bowel disease (IBD). However, the mechanism by which PXR provides protection remains unclear. Wild-type and Pxr-null mice were treated with agonist pregnenolone-16alpha-carbonitrile or vehicle administered 2.5% dextran sulfate sodium (DSS) drinking water induce IBD. Typical clinical symptoms evaluated on a daily basis. In vivo intestinal permeability assays proinflammatory cytokine analysis performed. agonist-treated protected from DSS-induced colitis compared vehicle-treated mice, as defined body weight loss, diarrhea, rectal bleeding, colon length, histology. Pregnenolone-16alpha-carbonitrile did not decrease severity of IBD mice. treatment increase epithelial barrier function but mRNA several NF-kappaB target genes PXR-dependent manner. The present study clearly demonstrates role for data suggest that PXR-mediated repression is critical activation decreases susceptibility