坏死性下垂
炎症体
细胞生物学
信号转导
活性氧
免疫学
生物
炎症
程序性细胞死亡
细胞凋亡
生物化学
作者
Haoyang Li,Jieying Guan,Jiaqian Chen,Weimin Sun,Honglv Chen,Yuhuan Wen,Qile Chen,Shiyun Xie,Xueyan Zhang,Ailin Tao,Jie Yan
标识
DOI:10.1016/j.bbadis.2022.166613
摘要
Pseudomonas aeruginosa induced acute lung injury is such a serious risk to public health, but the pathological regulation remains unclear. Here, we reported that PA mediated epithelial necroptosis plays an important role in pathological process. Pharmacological and genomic ablation of necroptosis signaling ameliorate PA mediated ALI and pulmonary inflammation. Our results further proved NLRP3 inflammasome to involve in the process. Mechanism investigation revealed the cross-talking between inflammasome activation and necroptosis that MLKL-dependent necroptosis signaling promotes the change of mitochondrial membrane potential for the release of reactive oxygen species (ROS), which is the important trigger for functional inflammasome activation. Furthermore, antioxidants such as Mito-TEMPO was confirmed to significantly restrain inflammasome activation in epithelium, resulting in a reduction in PA induced pulmonary inflammation. Taken together, our findings revealed that necroptosis-triggered NLRP3 inflammasome in epithelium plays a crucial role in PA mediated injury, which could be a potential therapeutic target for pulmonary inflammation.
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