The potential involvement of intestinal microsomal cytochrome P450 (P450) enzymes in protecting against colon inflammation and injury was studied in mice treated with dextran sulfate sodium (DSS) to induce colitis. Wild-type (WT) mice and mice with intestinal epithelium (IE)–specific deletion of the P450 reductase gene (IE-Cpr-null) were compared. DSS treatment caused more severe colon inflammation, as evidenced by the presence of higher levels of myeloperoxidase and proinflammatory cytokines, greater weight loss, colonic tissue damage, and colon shortening in IE-Cpr-null mice. The IE-Cpr-null mice were deficient in colonic corticosterone (CC) synthesis, as indicated by the inability of ex vivo–cultured colonic tissues from DSS-treated IE-Cpr-null mice to show increased CC production. These results suggest that microsomal P450 enzymes in the intestine play an important role in protecting colon epithelium from DSS-induced inflammation and injury, possibly through increased local CC synthesis response to DSS challenge.
See article at J Pharmacol Exp Ther 2015, 354:10–17.
- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics