Ma Wen-Jiang, Sun Yan-Hong, Jiang Jun-Xia, Dong Xin-Wei, Zhou Jian-Ying, Xie Qiang-Min
The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou 310009, China.
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China.
Prostaglandins Leukot Essent Fatty Acids. 2015 Mar;94:13-9. doi: 10.1016/j.plefa.2014.10.006. Epub 2014 Nov 4.
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.
作为对内皮细胞激活的响应，花生四烯酸可被细胞色素P450（CYP）环氧化酶转化为环氧二十碳三烯酸（EETs），其具有强大的血管舒张和抗炎特性。在本研究中，我们调查了外源性EETs对香烟烟雾提取物（CSE）诱导的人支气管上皮细胞（NCI-H292）炎症的影响。我们发现，CSE抑制CYP2C8的表达，并轻度刺激环氧水解酶2（EPHX2）的表达，但不改变CYP2J2的表达。用11,12-EET或14,15-EET处理可通过抑制p38丝裂原活化蛋白激酶（MAPKs）的磷酸化来减轻CSE诱导的白细胞介素（IL）-8释放。我们的结果表明，CSE可能通过降低EET水平来降低上皮细胞自身的抗炎能力。来自肺上皮细胞的EETs可能对上皮细胞损伤起关键的保护作用。
