| First Author | Ahlawat S | Year | 2014 |
| Journal | Sci Rep | Volume | 4 |
| Pages | 5551 | PubMed ID | 24989705 |
| Mgi Jnum | J:269051 | Mgi Id | MGI:6218397 |
| Doi | 10.1038/srep05551 | Citation | Ahlawat S, et al. (2014) Mice deficient in intestinal epithelium cytochrome P450 reductase are prone to acute toxin-induced mucosal damage. Sci Rep 4:5551 |
| abstractText | Cytochrome P450 (P450) enzymes are a superfamily of heme-containing enzymes involved in the metabolism of various endogenous compounds, including retinoids, glucocorticoids, and eicosanoids, that are postulated to participate in the maintenance and/or development of inflammatory and immune reactions in the intestinal mucosa. To investigate the role of P450 enzymes in intestinal inflammation and immunity, we took advantage of IE-Cpr-null mice, which are deficient in intestinal epithelium of NADPH-cytochrome P450 reductase (CPR), the obligate redox partner of all microsomal P450 enzymes. We report that IE-Cpr-null mice, following an acute toxin challenge, had higher levels of pro-inflammatory chemokines and increased tissue damage compared to wild-type mice. IE-Cpr-null mice had normal Peyer's patch numbers and elicited normal secretory IgA (SIgA) responses. However, SIgA baseline levels in IE-Cpr-null mice were consistently elevated over WT littermates. While neither retinoic acid nor glucocorticoid levels in serum and intestinal homogenates were altered in IE-Cpr-null mice, basal levels of arachidonic acid metabolites (11,12-DiHETE and 14,15-DiHETE) with known anti-inflammatory property were significantly lower compared to WT controls. Overall, these findings reveal immunological and metabolic changes resulting from a genetic deficiency in CPR expression in the intestine, and support a role for microsomal P450 enzymes in mucosal homeostasis and immunity. |
