Particulate matter 2.5 (PM2.5)-induced pulmonary inflammation has become a public concern in recent years. In which, the activation of the NLRP3/caspase-1 pathway was closely related to the inflammatory response of various diseases. However, the promotion effect of the NLRP3/caspase-1 pathway on PM2.5-induced pulmonary inflammation remains largely unclear. Here, our data showed that PM2.5 exposure caused lung injury in the mice by which inflammatory cell infiltration occurred in lung and alveolar structure disorder. Meanwhile, the exposure of human bronchial epithelial cells (16HBE) to PM2.5 resulted in suppressed cell viability, as well as elevated cell apoptosis. Moreover, a higher level of inflammatory cytokine and activation of the NLRP3/caspase-1 pathway in PM2.5-induced inflammation mice models and 16HBE cells. Mechanistically, pretreatment with MCC950, a NLRP3/caspase-1 pathway inhibitor, prevented PM2.5-induced lung injury, inflammatory response, and the number of inflammatory cells in BALFs, as well as promoted cell viability and decreased inflammatory cytokine secretion. Collectively, our findings indicated that the NLRP3/caspase-1 pathway serves a vital role in the pathological changes of pulmonary inflammation caused by PM2.5 exposure. MCC950 was expected to be the therapeutic target of PM2.5 inhalation mediated inflammatory diseases.

中文翻译：

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PM2 .5 通过激活 NLRP3 /caspase-1 信号通路诱导肺部炎症

近年来，颗粒物 2.5 (PM2.5) 引起的肺部炎症已成为公众关注的问题。其中，NLRP3/caspase-1通路的激活与多种疾病的炎症反应密切相关。然而，NLRP3/caspase-1 通路对 PM2.5 诱导的肺部炎症的促进作用仍不清楚。在这里，我们的数据显示 PM2.5 暴露导致小鼠肺损伤，其中炎症细胞浸润发生在肺和肺泡结构紊乱中。同时，人支气管上皮细胞 (16HBE) 暴露于 PM2.5 会导致细胞活力受到抑制，以及细胞凋亡增加。此外，在 PM2.5 诱导的炎症小鼠模型和 16HBE 细胞中，更高水平的炎症细胞因子和 NLRP3/caspase-1 通路的激活。从机制上讲，用 NLRP3/caspase-1 通路抑制剂 MCC950 预处理可预防 PM2.5 诱导的肺损伤、炎症反应和 BALF 中的炎症细胞数量，并促进细胞活力并减少炎症细胞因子的分泌。总的来说，我们的研究结果表明 NLRP3/caspase-1 通路在 PM2.5 暴露引起的肺部炎症的病理变化中起着至关重要的作用。MCC950 有望成为 PM2.5 吸入介导的炎症性疾病的治疗靶点。我们的研究结果表明，NLRP3/caspase-1 通路在 PM2.5 暴露引起的肺部炎症的病理变化中起着至关重要的作用。MCC950 有望成为 PM2.5 吸入介导的炎症性疾病的治疗靶点。我们的研究结果表明，NLRP3/caspase-1 通路在 PM2.5 暴露引起的肺部炎症的病理变化中起着至关重要的作用。MCC950 有望成为 PM2.5 吸入介导的炎症性疾病的治疗靶点。