单位：[1]Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China临床科室呼吸内科呼吸内科首都医科大学附属北京友谊医院[2]BeijingKey Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, ChineseAcademy of Medical Sciences and Peking Union Medical College, Beijing, China
Epoxyeicosatrienoic acids (EETs) are metabolic products of free arachidonic acid, which are produced through cytochrome P-450 (CYP) epoxygenases. EETs have anti-inflammatory, antiapoptotic, and antioxidative activities. However, the effect of EETs on cigarette smoke-induced lung inflammation is not clear. Autophagy is believed to be involved in the pathogenesis of chronic obstructive pulmonary disease. In addition, nuclear erythroid-related factor 2 (Nrf2), a transcription factor that regulates many antioxidant genes, is thought to regulate antioxidant defenses in several lung diseases. In addition, interaction between EETs, autophagy, and Nrf2 has been reported. The aim of this study was to explore the effect of 14,15-EET on cigarette smoke condensate (CSC)-induced inflammation in a human bronchial epithelial cell line (Beas-2B), and to determine whether the underlying mechanisms involved in the regulation of Nrf2 through inhibition of autophagy. Autophagy and expression of autophagy signaling pathway proteins (LC3B, p62, PI3K, Akt, p-Akt, and p-mTOR) and anti-inflammatory proteins (Nrf2 and HO-1) were assessed via Western blot analysis. Autophagosomes and autolysosomes were detected by adenoviral mRFP-GFP-LC3 transfection. Inflammatory factors (IL-6, IL-8, and MCP-1) were detected by ELISA. Lentiviral vectors carrying p62 short hairpin RNA were used to interfere with p62 expression to evaluate the effect of p62 on Nrf2 expression. Nrf2 expression was determined through immunocytochemistry. 14,15-EET treatment resulted in a significant reduction in IL-6, IL-8, and MCP-1 secretion, and increased accumulation of Nrf2 and expression of HO-1. In addition, 14,15-EET inhibited CSC-induced autophagy in Beas-2B cells. The mechanism of the anti-inflammatory effect of 14,15-EET involved inhibition of autophagy and an increase in p62 levels, followed by translocation of Nrf2 into the nucleus, which then upregulated expression of the antioxidant enzyme HO-1. 14,15-EET protects against CSC-induced lung inflammation by promoting accumulation of Nrf2 via inhibition of autophagy.
基金：
Beijing Municipal Natural Science FoundationBeijing Natural Science Foundation [7142046, 7164250]; Beijing Municipal Health Bureau Grant [Shou Fa 2011hyphen2002-03]
第一作者单位：[1]Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[1]Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China[*1]Dept. of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical Univ., No. 95 Yong An Road, Xichen District, Beijing 100050, China
推荐引用方式(GB/T 7714)：
Li Yunxiao,Yu Ganggang,Yuan Shaopeng,et al.14,15-Epoxyeicosatrienoic acid suppresses cigarette smoke condensate-induced inflammation in lung epithelial cells by inhibiting autophagy[J].AMERICAN JOURNAL of PHYSIOLOGY-LUNG CELLULAR and MOLECULAR PHYSIOLOGY.2016,311(5):L970-L980.doi:10.1152/ajplung.00161.2016.
APA：
Li, Yunxiao,Yu, Ganggang,Yuan, Shaopeng,Tan, Chunting,Xie, Jianlin...&Wang, Haoyan.(2016).14,15-Epoxyeicosatrienoic acid suppresses cigarette smoke condensate-induced inflammation in lung epithelial cells by inhibiting autophagy.AMERICAN JOURNAL of PHYSIOLOGY-LUNG CELLULAR and MOLECULAR PHYSIOLOGY,311,(5)
MLA：
Li, Yunxiao,et al."14,15-Epoxyeicosatrienoic acid suppresses cigarette smoke condensate-induced inflammation in lung epithelial cells by inhibiting autophagy".AMERICAN JOURNAL of PHYSIOLOGY-LUNG CELLULAR and MOLECULAR PHYSIOLOGY 311..5(2016):L970-L980
