title: Pregnane X receptor is required for IFN-α-mediated CYP3A29 expression in pigs.
abstract: Pregnane X receptor (PXR) has been identified as a central mediator for coordinate responses to xenobiotic and drug metabolism, and is the major transcriptional regulator of cytochrome P-450 (CYP). Interferon (IFN)-α is known to induce antiviral mechanisms and exert immune regulatory capacity in various cell types. Here, we used primary porcine hepatocytes and a cultured hepatocyte cell line to identify the metabolic role of PXR in IFN-α-mediated CYP3A29 expression. We found that IFN-α could activate PXR in both time- and dose-dependent manners in pigs. Activation of PXR significantly increased CYP3A29 mRNA and protein expression. Meanwhile, the expression of CYP3A29 induced by IFN-α occurred after the increase of PXR expression in porcine hepatocytes. In addition, the IFN-α-induced CYP3A29 expression was blocked by PXR knockdown. The PXR-overexpressed cells (transfected with porcine PXR) increased CYP3A29 mRNA and protein expression. Furthermore, in animal experiments, we found that IFN-α increased both CYP3A29 mRNA and protein levels. Collectively, our results suggest that PXR plays an important role in IFN-α-mediated CYP3A29 expression in porcine hepatocytes.
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors: Xiaowen
authors: X
authors: Li
authors: Hubei Provincial Institute of Veterinary Drug Control, Wuhan 430068, PR China.
authors: Xiue
authors: X
authors: Jin
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors: Xiaoqiao
authors: X
authors: Zhou
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: wxl070@mail.hzau.edu.cn.
authors: Xiliang
authors: X
authors: Wang
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors: Deshi
authors: D
authors: Shi
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China.
authors: Yuncai
authors: Y
authors: Xiao
authors: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: bidingren@mail.hzau.edu.cn.
authors: Dingren
authors: D
authors: Bi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D016898:Interferon-alpha / Q000276:immunology*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics / Q000276:immunology*; D013552:Swine; D015533:Transcriptional Activation
chemical_list: D016898:Interferon-alpha; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D051544:Cytochrome P-450 CYP3A
keywords: CYP3A29; Cytochrome P450; Interferon (IFN)-α; Pig; Pregnane X receptor