title: Glucocorticoid receptor contributes to the altered expression of hepatic cytochrome P450 upon cigarette smoking.
abstract: Cigarette smoking has been shown to cause pathological alterations in the liver. However, how hepatic metabolism is altered during cigarette smoking‑induced inflammation remains to be fully elucidated. In the present study, a rat model of smoking was established to examine the effects of cigarette smoking on inflammation, autophagy activity, and the expression of nuclear receptor and CYP in the liver. Elevated expression of interleukin 1β and activation of autophagy in the liver were observed upon smoking exposure in rats. Cigarette smoking induced a significant reduction in the mRNA expression levels of cytochromes, including cytochrome P450 (Cyp)1A2, Cyp2D4 and Cyp3A2. Accordingly, a decrease was also observed in glucocorticoid receptor (GR), a regulator of the expression of Cyp. Activation of the GR signal in human hepatic LO2 cells did not affect autophagic genes, however, it led to the upregulation of hCYP1A2, hCYP2C19 and hCYP3A4, and the downregulation of hCYP2C9. The GR antagonist, RU486, eliminated this effect, suggesting the importance of GR in liver metabolism upon cigarette smoking.
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Zhongfang
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Subei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Respiratory, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Respiratory, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Junping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Respiratory, Tianjin Medical University General Hospital, Tianjin 30005, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Ning
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of The Chinese Academy of Sciences, Shanghai 200031, P.R. China.
authors.forename: Zhixue
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Basic Medicine Laboratory, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin 300350, P.R. China.
authors.forename: Huaiyong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012907:Smoking
chemical_list: D053583:Interleukin-1beta; D007527:Isoenzymes; D011965:Receptors, Glucocorticoid; D003577:Cytochrome P-450 Enzyme System