Activation of MAPKs influences the expression of drug-metabolizing enzymes in primary human hepatocytes.

We examined the effects of model activators of mitogen-activated protein kinases (MAPKs) on basal and rifampicin-, phenobarbital- and dioxin-inducible expression of phase I and phase II biotransformation enzymes in primary human hepatocytes. Cells were treated for 24 h with sorbitol (SOR), anisomycin (ANI) and epidermal growth factor (EGF) in the presence or absence of inducers. The levels of CYP1A1, CYP1A2, CYP2B6, CYP3A4, UGT1A1, UGT2B17, SULT1A1, SULT2A1, SULT1B2, GSTA1, GSTA2 mRNAs were determined. SOR and EGF inhibited the expression of the tested genes, while ANI had no effect. We conclude that MAPKs play important role in the transcriptional regulation of drug-metabolizing enzymes.