Complement regulatory protein CD46 induces autophagy against oxidative stress-mediated apoptosis in normal and asthmatic airway epithelium

Yi Giien Tsai, Yung Sung Wen, Jiu Yao Wang, Kuender D. Yang, Hai Lun Sun, Jia Hung Liou, Ching Yuang Lin

研究成果: Article

6 引文 斯高帕斯(Scopus)

摘要

Autophagy plays a major role in defending against oxidative stress in respiratory epithelial cells. The complement regulatory protein CD46 can enhance autophagy and decrease local complement activation at sites of inflammation. This study investigated the mechanism by which CD46 protects against oxidative stress-mediated apoptosis in respiratory epithelium in asthmatic patients. Nasal mucosa samples were obtained from 60 adults with mild asthma who received turbinectomy and 30 controls. A decreased expression of CD46 and increased apoptosis were noted in the damaged nasal epithelium from the asthmatic patients. Primary epithelial cells cultured with Dermatophagoides pteronyssinus 2 showed decreased CD46 and increased cleaved CASPASE-3A expressions. Crosslinking CD46 mAb could induce the formation of autophagosomes and LC3-II expression in primary epithelial cells. CD46 engagement could induce autophagy against hydrogen peroxide-induced epithelial cell death, whereas the autophagy inhibitor 3-methyladenine decreased this effect. In addition, CD46 engagement decreased the expressions of PRO-IL-1β and NLRP3, enhanced the expression of scaffold protein GOPC, and diminished hydrogen peroxide-induced 8-OHdG, IL-1β and IL-6 production. Silencing ATG5 in human lung epithelial A549 cells decreased CD46-activated autophagy with LC3-II. CD46 induced autophagy and decreased the oxidative stress-mediated apoptosis of respiratory epithelium, and this may offer a new therapeutic strategy to treat asthma.

原文English
文章編號12973
期刊Scientific reports
8
發行號1
DOIs
出版狀態Published - 2018 十二月 1

All Science Journal Classification (ASJC) codes

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