title: Epoxyeicosatrienoic acids attenuate cigarette smoke extract-induced interleukin-8 production in bronchial epithelial cells.
abstract: In response to endothelial cell activation, arachidonic acid can be converted by cytochrome P450 (CYP) epoxygenases to epoxyeicosatrienoic acids (EETs), which have potent vasodilator and anti-inflammatory properties. In this study, we investigated the effects of exogenous EETs on cigarette smoke extract (CSE)-induced inflammation in human bronchial epithelial cells (NCI-H292). We found that CSE inhibited the expression of CYP2C8 and mildly stimulated the expression of epoxide hydrolase 2 (EPHX2) but did not change the expression of CYP2J2. Treatment with 11,12-EET or 14,15-EET attenuated the CSE-induced release of interleukin (IL)-8 by inhibiting the phosphorylation of p38 mitogen-activated protein kinases (MAPKs). Our results demonstrated that CSE may reduce the anti-inflammatory ability of epithelial cells themselves by lowering the EET level. EETs from pulmonary epithelial cells may play a critical protective role on epithelial cell injury.
authors.affiliation: The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, China.
authors.forename: Wen-Jiang
authors.initials: WJ
authors.lastname: Ma
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Sun
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Jiang
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Dong
authors.affiliation: The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, China. Electronic address: Drzjy@163.com.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhou
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China; Laboratory Animal Center of Zhejiang University, Hangzhou 310058, China. Electronic address: xieqm@zju.edu.cn.
authors.forename: Qiang-Min
authors.initials: QM
authors.lastname: Xie
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002460:Cell Line; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; C000717350:CYP2J2 protein, human; D016209:Interleukin-8; D014665:Vasodilator Agents; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; D015126:8,11,14-Eicosatrienoic Acid
keywords: Bronchial epithelial cells; CYP2C8; Epoxyeicosatrienoic acids; Interleukin-8; MAPK