Interleukin-2 overexpresses c-myc and down-regulates cytochrome P-450 in rat hepatocytes.
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Tinel M, Elkahwaji J, Robin MA, Fardel N, Descatoire V, Haouzi D, Berson A, Pessayre D
Interleukin-2 overexpresses c-myc and down-regulates cytochrome P-450 in rat hepatocytes.
J Pharmacol Exp Ther. 1999 May;289(2):649-55.
- PubMed ID
- 10215635 [ View in PubMed]
- Abstract
The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) decreases cytochrome P-450 (CYP) expression in rat hepatocytes. Because IL-2 increases c-Myc in lymphocytes and because c-myc overexpression represses several genes, we postulated that the IL-2/IL-2R interaction may increase c-Myc and thereby down-regulate CYP in hepatocytes. Cultured rat hepatocytes were exposed for 24 h to IL-2 (350 U/ml) and other agents. IL-2 increased c-myc mRNA and protein but decreased total CYP and the mRNAs and proteins of CYP2C11 and CYP3A. The IL-2-mediated c-myc overexpression and CYP down-regulation were prevented by 1) genistein (a tyrosine kinase inhibitor that blocks the initial transduction of the IL-2R signal), 2) retinoic acid, butyric acid, or dimethyl sulfoxide (three agents that block c-myc transcription), or 3) an antisense c-myc oligonucleotide (which may cause rapid degradation of the c-myc transcript). It is concluded that IL-2 causes the overexpression of c-myc and the down-regulation of CYPs in rat hepatocytes. Block of c-myc overexpression, at three different levels with five different agents, prevents CYP down-regulation, suggesting that c-myc overexpression may directly or indirectly repress CYP in hepatocytes.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Dimethyl sulfoxide Myc proto-oncogene protein Protein Humans UnknownDownregulatorDetails