Modulation of Hepatic P450, Cytokine and Acute Phase Protein mRNAs by C. rodentium Infection in Interleukin‐6‐ and Interferon‐γ‐null Mice

Abstract

Following infection with Citrobacter rodentium, the equivalent of enteropathogenic E. coli in humans, murine hepatic cytochrome P450 mRNAs are selectively regulated and serum pro‐inflammatory cytokines including interleukin‐6 (IL6) and interferon‐γ (IFNγ) are elevated. In this study, female C57BL/6 (WT), IL6‐null or IFNγ‐null mice were infected orally with C. rodentium and the hepatic expression of several P450, cytokine and acute phase protein mRNAs were examined 7 days later. CYP1A2, CYP2A5 and IL6 mRNAs were unchanged in any of the groups. CYP2B9, 2E1, 4A10 and 4A14 were reduced to 22 to 74% of control levels, and CYP2D9 and tumor necrosis factor‐α mRNAs were induced 2 and 14‐fold respectively, and these effects were similar in all three groups. In WT and IL6‐null mice, mRNA levels of CYP2D22, 3A25 and angiotensinogen were reduced to between 55 and 65% of control levels and interleukin‐1 levels were induced by infection; whereas, mRNA levels remained unchanged in IFNγ‐null mice. CYP3A13 mRNA was reduced to 69% of control in infected IL6‐null but not in WT or IFNγ‐null mice. Up‐regulation of α‐fibrinogen and down‐regulated levels of CYP3A11 mRNAs were observed in WT mice while the levels of these mRNAs were unchanged in either IL6‐ or IFNγ‐null animals. These results indicate roles for both IL‐6 and IFNγ in regulation of CYP3A and 2D22 mRNAs during C. rodentium infection. This work was supported by NIH grant DK072372.