Hepatic Cytochrome P450 Expression during Citrobacter Rodentium Infection in Tumor Necrosis Factor Receptor p55‐/‐ Mice

Abstract

Citrobacter rodentium is the rodent equivalent of enteropathogenic Escherichia coli infection in humans. The proinflammatory cytokine tumor necrosis factor‐α (TNFα) is induced in mice during C. rodentium infection and may be involved in regulating cytochrome P450 (P450) expression during inflammation. In this study, female mice lacking the gene for the p55 receptor for TNFα, as well as their C57BL/6 controls, were orally infected with C. rodentium and sacrificed 7 days later. CYP2B9 and 3A41 mRNA levels were down‐regulated, and CYP2D22, 3A11 and 3A13 mRNA levels remained near control levels in both the C57BL/6 and the TNF p55 ‐/‐ mice. Hepatic CYP4A10 and 4A14 mRNAs were down‐regulated more (less than 20% of control) in the TNF p55‐/‐ mice than in the C57BL/6 mice, (50% of control). Similarly, CYP2D9 mRNA levels were more highly induced in TNF p55 ‐/‐ (18‐fold) than in C57Bl/6 (2‐fold) mice, although CYP2D protein levels were near control expression levels for both strains. CYP2E1 and 3A25 displayed similar trends in which their mRNA levels were down‐regulated only in the C57BL/6 but not in the TNF p55‐/‐ mice. CYP2E1 protein expression levels followed the same trend as its mRNA. The data suggest that TNFα may play a role in down‐regulating specific hepatic P450s during C. rodentium infection. Supported by NIH grant DK072372.