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 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.
Calleja
C
C
Laboratoire de Pharmacologie-Toxicologie INRA, Toulouse, France.
Eeckhoutte
C
C
Larrieu
G
G
Dupuy
J
J
Pineau
T
T
Galtier
P
P
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
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