DIFFERENTIAL-EFFECTS OF INTERLEUKIN-1-BETA, INTERLEUKIN-2, AND INTERFERON-GAMMA ON THE INDUCIBLE EXPRESSION OF CYP 1A1 AND CYP 1A2 IN CULTURED RABBIT HEPATOCYTES

The effects of interleukin-1 beta, interleukin-2 and interferon-gamma and their combinations were investigated on induced cytochrome P 4501A of cultured rabbit hepatocytes considered 72 h after plating. Without apparent cellular toxicity, these cytokines provoke a significant dec rease in TBZ- and BNF-induced P4501A1/2 expression, However specific p atterns of action are revealed : IL-1 beta is the most potent cytokine in regard to CYP1A1/2 mRNA suppression whereas IL-2 exerts repressive effects only on P4501A1 induced expression. Although being a strong i nhibitor of induced enzymatic activities and protein contents, IFN-gam ma exhibits only a weak influence on CYP1A1/2 mRNAs with the exception of its association with interleukins. All these results suggest that IL-1 beta and IL-2 promote mainly a transcriptional repression mechani sm whereas IFN-gamma would stimulate a post-transcriptional suppressiv e pathway. (C) 1997 Academic Press.