title: 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.
abstract: 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 decrease in TBZ- and BNF-induced P4501A1/ 2 expression. However specific patterns 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 inhibitor of induced enzymatic activities and protein contents, IFN-gamma 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 transcriptional repression mechanism whereas IFN-gamma would stimulate a post-transcriptional suppressive pathway.
authors.affiliation: Laboratoire de Pharmacologie-Toxicologie INRA, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Calleja
authors.forename: C
authors.initials: C
authors.lastname: Eeckhoutte
authors.forename: G
authors.initials: G
authors.lastname: Larrieu
authors.forename: J
authors.initials: J
authors.lastname: Dupuy
authors.forename: T
authors.initials: T
authors.lastname: Pineau
authors.forename: P
authors.initials: P
authors.lastname: Galtier
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013827:Thiabendazole / Q000494:pharmacology; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D000969:Antinematodal Agents; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D019324:beta-Naphthoflavone; D007371:Interferon-gamma; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D013827:Thiabendazole