Differential Effects of Interleukin-1β, Interleukin-2, and Interferon-γ on the Inducible Expression of CYP 1A1 and CYP 1A2 in Cultured Rabbit Hepatocytes

• Published in: Biochemical and biophysical research communications 1997-10, Vol.239 (1), p.273-278
• Main Authors: Calleja, Cécile, Eeckhoutte, Claudine, Larrieu, Gilberte, Dupuy, Jacques, Pineau, Thierry, Galtier, Pierre
• Format: Article
• Language: English
• Subjects: Animals; Antinematodal Agents - pharmacology; beta-Naphthoflavone - pharmacology; Biochemistry, Molecular Biology; Cells, Cultured; Cytochrome P-450 CYP1A1 - biosynthesis; Cytochrome P-450 CYP1A2 - biosynthesis; Enzyme Induction; Enzyme Inhibitors - pharmacology; Interferon-gamma - pharmacology; Interleukin-1 - pharmacology; Interleukin-2 - pharmacology; Life Sciences; Liver - enzymology; Male; Rabbits; Receptors, Aryl Hydrocarbon - metabolism; RNA, Messenger - metabolism; Thiabendazole - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1997.7468

The effects of interleukin-1β, interleukin-2 and interferon-γ 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 decrease in TBZ- and BNF-induced P4501A1/2 expression. However specific patterns of action are revealed : IL-1β 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 inhibitor of induced enzymatic activities and protein contents, IFN-γ exhibits only a weak influence on CYP1A1/2 mRNAs with the exception of its association with interleukins. All these results suggest that IL-1β and IL-2 promote mainly a transcriptional repression mechanism whereas IFN-γ would stimulate a post-transcriptional suppressive pathway.