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

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.