三氯生通过诱导巨噬细胞非mTOR途径自噬加强胞内菌杀伤  

Enhancement of Intracellular Bacteria Killing Ability in Macrophages by Triclosan-induced Autophagy via a TOR-independent Pathway

作　　者：施晓晨 孙青松[2] 安雅男 张巧丽[1] 郭娜[3] 于录[1] 

机构地区：[1]吉林大学动物医学学院人兽共患病研究所,人兽共患病研究教育部重点实验室,长春130062 [2]吉林农业科技学院动物科技学院,吉林132101 [3]吉林大学军需科技学院,长春130062

出　　处：《吉林农业大学学报》2016年第2期212-217,239,共7页Journal of Jilin Agricultural University

基　　金：国家“十二五”重大传染病专项课题(2012ZX10003002);国家自然科学基金项目(31172364;31271951;31000822);教育部新世纪人才计划项目(NCET-09-0431;NCET-13-0245);吉林农业科技学院博士启动基金项目[吉农院合字(2015)第243号]

摘　　要：为了研究三氯生能否引起细胞自噬并探讨其可能的诱导通路,揭示三氯生作为抗菌药物的新作用机制,利用免疫荧光、菌落计数、免疫印迹等技术检测经三氯生处理过细胞的自噬水平、相关蛋白表达量的变化及杀菌能力的改变。结果表明:三氯生能引起Hela细胞和Raw264.7细胞的自噬,并且该自噬为完全自噬。三氯生诱导的小鼠巨噬细胞系Raw264.7细胞自噬依赖的是胞外信号调节激酶(Extracellular signal-regulated kinase,ERK)途径,而非经典的雷帕霉素靶蛋白(Mammalian target of rapamycin,m TOR)途径。此外,三氯生通过该作用机制加强了巨噬细胞对胞内菌的杀伤作用。研究表明,三氯生诱导自噬的现象在细胞中普遍存在,自噬在对抗病原微生物中起到重要作用,诱导自噬是三氯生作为抗菌药物的新作用机制。Whether triclosan can induce autophagy in cells is not clear,and therefore,the possible mechanism remains unknown,either. To reveal the new antibacterial mechanism of triclosan,we used immunofluorescent staining,bacterial colony counts and Western Blot assays to detect the levels of autophagy,the expressions of relevant proteins and the variation of bacteria killing ability in triclosan-treated cells. The results demonstrated that triclosan could indeed induce autophagy in Hela cells and Raw264. 7 cells. Furthermore,the triclosan-induced autophagy was a complete process.Triclosan induced autophagy via an ERK-dependent rather than a mT OR-dependent pathway. Moreover,it was triclosan-induced autophagy that enhanced the abilities of intracellular bacteria killing in macrophages. In conclusion,triclosan-induced autophagy generally existed in mammalian cells.Since autophagy played a vital role in combating with pathogens,autophagy induction was a new mechanism for triclosan to fight against bacteria.

关 键 词：三氯生 巨噬细胞 MTOR ERK 胞内菌杀伤 

分 类 号：R966[医药卫生—药理学]