title: IFN-γ regulates cytochrome 3A29 through pregnane X receptor in pigs.
abstract: 1. The expression and the activity of cytochromes P450 (CYPs) can be elevated by the activation of nuclear receptors. The pregnane X receptor (PXR, or nuclear receptor NR1I2) is a ligand-activated transcription factor that mediates responses to diverse xenobiotics and endogenous chemicals. Here we investigated the regulatory role of PXR in IFN-γ-mediated CYP3A29 expression in pig liver microsomes, primary porcine hepatocytes, and a cultured hepatocyte cell line. 2. IFN-γ significantly up-regulated CYP3A29 and PXR expressions at mRNA and protein levels in a dose-dependent manner. IFN-γ treatment significantly increased the metabolism of nifedipine. PXR and IFN-γ treatments significantly enhanced the activity of CYP3A29 promoter and the upstream region from -1473 to -1021 of CYP3A29 might be PXR-binding site. Moreover, the IFN-γ-induced CYP3A29 expression was blocked by PXR knockdown, whereas CYP3A29 mRNA and protein expression levels were dramatically elevated by PXR overexpression. 3. The regulatory effect of IFN-γ on CYP3A29 expression is mediated via PXR.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , PR China .
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Li
authors.forename: Xiuzhong
authors.initials: X
authors.lastname: Hu
authors.forename: Xiue
authors.initials: X
authors.lastname: Jin
authors.forename: Xiaoqiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiliang
authors.initials: X
authors.lastname: Wang
authors.forename: Deshi
authors.initials: D
authors.lastname: Shi
authors.forename: Dingren
authors.initials: D
authors.lastname: Bi
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D022781:Hepatocytes / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D034421:Sus scrofa / Q000378:metabolism*
chemical_list: D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid; D007371:Interferon-gamma; D051544:Cytochrome P-450 CYP3A
keywords: CYP3A29; Cytochrome P450; interferon-γ; pig; pregnane X receptor