Acinetobacter baumannii outer membrane protein A induces HeLa cell autophagy via MAPK/JNK signaling pathway
Acinetobacter baumannii outer membrane protein A induces HeLa cell autophagy via MAPK/JNK signaling pathway
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DOI：
10.1016/j.ijmm.2018.12.004
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发表时间：
2019-03-01
影响因子：
4.1
通讯作者：
Ding, Wenyi
中科院分区：
文献类型：
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作者：
An, Zhiyuan;Huang, Xiaoxi;Ding, Wenyi
自噬是一种进化保守的自我平衡过程，通过清除受损的细胞器和错误折叠的蛋白质，在维持细胞内环境稳定中发挥重要作用。免疫触发的自噬特异性地抑制细胞内细菌复制的侵入，从而保护细胞免受微生物感染。有报道称鲍曼不动杆菌可引发细胞自噬。然而，其毒力蛋白OmpA的作用仍不清楚。因此，本研究旨在探讨鲍曼不动杆菌OmpA对细胞自噬的影响及其分子机制。结果显示，OmpA诱导HeLa和RAW264.7细胞自噬，增加LC 3BII表达，并阻碍p62降解。此外，OmpA通过干扰自噬体与溶酶体的融合而触发不完全自噬。此外，OmpA激活MAPK/JNK信号通路，增强JNK、p38和ERIC、c-Jun的磷酸化水平，抑制JNK信号通路可抑制OmpA诱导的HeLa细胞自噬。携带OmpA的Ab野生型菌株引发不完全自噬并导致大量IL-1 β产生。Ab-Delta OmpA菌株（OmpA基因突变）恢复了HeLa细胞中的自噬通量并减少了p62的积累和IL-1 β的释放。雷帕霉素激活自噬以抑制OmPA诱导的IL-1 β分泌并保护HeLa细胞免受炎症损伤。这些结果表明OmpA可以通过MAPK/JNK信号通路诱导HeLa细胞自噬。用雷帕霉素预处理激活自噬并防止细胞死亡。
Autophagy is an evolutionary conserved self-balancing process that plays an important role in maintaining cellular homeostasis via the clearance of damaged organelles and misfolded proteins. Infection-triggered autophagy specifically inhibits the invasion of intracellular bacterial replication and hence protects the cells from microbial infections. It has been reported that Acinetobacter baumannii trigger cell autophagy. However, the role of its virulence protein OmpA remains unclear. Therefore, this study aimed to explore the effects of Acinetobacter baumannii OmpA on cell autophagy and its underlying molecular mechanisms. The results showed that OmpA induced autophagy in HeLa and RAW264.7 cells, increased LC3BII expression, and hindered p62 degradation. Moreover, OmpA triggered incomplete autophagy by interfering the fusion of autophagosomes with lysosomes. Besides, OmpA activated MAPK/JNK signaling pathway and enhanced the phosphorylation levels of JNK, p38, and ERIC, c-Jun. Inhibition of JNK signaling pathway suppressed OmpA-induced autophagy in HeLa cells. Ab wild-type strains carrying OmpA triggered incomplete autophagy and resulted in a large number of IL-1 beta production. Ab-Delta OmpA strain (OmpA gene mutation) restored autophagic flux and reduced the accumulation of p62 and the release of IL-1 beta in HeLa cells. Rapamycin activated autophagy to inhibit OmpA-induced IL-1 beta secretion and protect HeLa cells from inflammatory damage. Collectively, these results suggest that OmpA can induce autophagy in HeLa cells through MAPK/JNK signaling pathway. Pre-treatment with Rapamycin activates autophagy and protects against cell death.