Influence of cytokines on the regulation of mouse hepatic cytochrome P450 2A5 expression

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Gilmore, William James
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University of Guelph

Murine cytochrome P450 2A5 (CYP2A5) is induced during hepatotoxicity and hepatitis, conditions which are generally associated with depression of hepatic CYPs. This study investigated the influence of non-parenchymal liver cells and pro-inflammatory cytokines on the regulation of hepatic CYP2A5 expression. Individual pro-inflammatory cytokines IL-1β, IL-6, TNF-α, TGF-β, and IFN-γ, did not influence CYP2A5 mRNA expression in cultured primary mouse hepatocytes. Non-parenchymal cells which may release cytokines during hepatic injury also did not contribute to CYP2A5 mRNA induction in pyrazole-treated hepatocyte cultures. A reduction in CYP2A5 mRNA levels was observed in lipopolysaccharide-treated (LPS) cultures and also in LPS-treated mice. Serum alanine aminotransferase levels were elevated in mice treated with pyrazole at a dose that resulted in an induction of CYP2A5. These results demonstrate that treatment with various pro-inflammatory cytokines and LPS does not increase CYP2A5 expression in mouse hepatocytes suggesting that hepatotoxicity, rather than hepatitis, is required for the induction of CYP2A5.

murine cytochrome P450 2A5 (CYP2A5), non-parenchymal liver cells, pro-inflammatory cytokines, regulation, hepatic CYP2A5 expression