Study of protective role of Cytochrome P450s in inflammatory bowel disease using Cprlow mouse model
Xiaoyu Fan · 2014
Glucocorticoids (GCs) are potent regulatory factors for inflammation. The synthesis of GCs involves several cytochrome P450 enzymes, such as mitochondrial CYP11A1, CYP11B1, and microsomal CYP21. Previous studies have indicated that the GCs, including those released from adrenal glands, and those synthesized in extra-adrenal tissues, such as intestine, exert inhibitory effects on inflammatory bowel disease (IBD). In a previous study using an intestinal epithelium (IE)-specific P450 reductase (CPR) knockout (IE-Cpr-null) mouse model, the results suggested that the intestinal P450s had a protective role in DSS-induced acute colitis. In this study, using a hypomorphic CPR mouse model (Cprlow), which presents a global 74-95 % decreased expression of CPR, we have found that there were more severe lesions after DSS treatment in the colon of Cprlow mouse model, compared with B6 mice, based on gross examination, histopathological analysis, and disease activity index. Our results confirm the protective role of intestinal cytochrome P450s in IBD.