title: Up-regulation of glutathione S-transferases alpha by interleukin 4 in human hepatocytes in primary culture.
abstract: During inflammation and infection, overexpression of cytokines is associated with changes in cytochrome P450 (CYP) activities. The present study investigated the effect of cytokines on expression of the glutathione S-transferases (GST), phase II enzymes, involved in drug detoxication and in protection against lipid peroxidation. Human hepatocytes in primary culture were exposed to interleukin 6 (IL6), a proinflammatory cytokine and interleukin 4 (IL4) thought to be an anti-inflammatory cytokine and known to induce CYP2E1 specifically. After a three-day treatment, no reproducible effects of IL-6 could be demonstrated on either GSTA1 and/or A2 or M1 mRNA levels (GSTA1 and A2 were not discriminated by the cDNA probe). In contrast, GSTA1 and/or A2 mRNAs and GSTA1 and A2 proteins were reproducibly increased after IL4 treatment. This increase was blocked by alpha-amanitin, suggesting that active transcription is necessary and was associated with increased AP1 binding activities. These results provide evidences that IL4 exerts important effects on detoxifying hepatic drug metabolizing enzymes.
mesh_terms: D000328:Adult; D000546:Amanitins / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000546:Amanitins; D015850:Interleukin-6; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D015847:Interleukin-4; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D005982:Glutathione Transferase