Epoxyeicosatrienoic acids attenuate cigarette smoke extract-induced interleukin-8 production in bronchial epithelial cells

Wen-Jiang Ma; Yan-Hong Sun; Jun-Xia Jiang; Xin-Wei Dong; Jian-Ying Zhou; Qiang-Min Xie

doi:10.1016/j.plefa.2014.10.006

Epoxyeicosatrienoic acids attenuate cigarette smoke extract-induced interleukin-8 production in bronchial epithelial cells

Prostaglandins Leukot Essent Fatty Acids. 2015 Mar:94:13-9. doi: 10.1016/j.plefa.2014.10.006. Epub 2014 Nov 4.

Authors

Wen-Jiang Ma¹, Yan-Hong Sun², Jun-Xia Jiang², Xin-Wei Dong², Jian-Ying Zhou³, Qiang-Min Xie⁴

Affiliations

¹ The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, China.
² Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
³ The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, China. Electronic address: Drzjy@163.com.
⁴ 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.

PMID: 25467970
DOI: 10.1016/j.plefa.2014.10.006

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.

Keywords: Bronchial epithelial cells; CYP2C8; Epoxyeicosatrienoic acids; Interleukin-8; MAPK.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

8,11,14-Eicosatrienoic Acid / analogs & derivatives
8,11,14-Eicosatrienoic Acid / pharmacology*
Anti-Inflammatory Agents / pharmacology*
Bronchi / cytology*
Bronchi / drug effects
Cell Line
Cytochrome P-450 CYP2J2
Cytochrome P-450 Enzyme System / genetics
Cytochrome P-450 Enzyme System / metabolism
Epithelial Cells / cytology
Epithelial Cells / drug effects*
Gene Expression Regulation / drug effects
Humans
Interleukin-8 / genetics*
Interleukin-8 / metabolism
MAP Kinase Signaling System / drug effects
Smoking / adverse effects*
Vasodilator Agents / pharmacology

Substances

Anti-Inflammatory Agents
CYP2J2 protein, human
Interleukin-8
Vasodilator Agents
11,12-epoxy-5,8,14-eicosatrienoic acid
14,15-epoxy-5,8,11-eicosatrienoic acid
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP2J2
8,11,14-Eicosatrienoic Acid