College of Medical Laboratory, Dalian Medical University, Dalian, Liaoning Province, 116044, People's Republic of China.
College of Medical Laboratory, Dalian Medical University, Dalian, Liaoning Province, 116044, People's Republic of China; Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.
Biomed Pharmacother. 2020 Oct;130:110481. doi: 10.1016/j.biopha.2020.110481. Epub 2020 Jul 14.
PM, a main particulate air pollutant, poses a serious hazard to human health. The exposure to PM increases mortality and morbidity of many respiratory diseases such as asthma, chronic obstructive pulmonary diseases and even lung cancer. The contribution of reactive oxygen species (ROS) in the PM-induced acute lung injury process was confirmed in our previous research, but the molecular mechanism based for it remains unclarified. In this research, ROS-induced lung injury after exposure to PM was explored in vivo and in vitro. The in vivo study indicated that N-acetyl-L-cysteine (NAC) could attenuate the accumulation of inflammatory cells, the thickening of alveolar wall and the degree of lung injury. Furthermore, we found ROS could regulate the intracellular Ca level, expression of the Transient Receptor Potential Melastatin 2 (TRPM2), NLRP3 and its downstream inflammatory factors in vivo. In vitro experiments with A549 cells and primary type II alveolar epithelium cells (SD cells) showed that ROS induced by PM exposure could mediate intracellular Ca mobilization via TRPM2, with a subsequent activation of NLRP3. In our present study, we demonstrated the contribution of the ROS-TRPM2-Ca-NLRP3 pathway in PM-induced acute lung injury and offered a potential therapeutical target valid for related pathology.
PM，一种主要的空气颗粒物污染物，对人类健康构成严重威胁。暴露于 PM 会增加许多呼吸道疾病（如哮喘、慢性阻塞性肺疾病，甚至肺癌）的死亡率和发病率。我们之前的研究已经证实，活性氧（ROS）在 PM 诱导的急性肺损伤过程中起作用，但它的分子机制仍不清楚。在这项研究中，我们在体内和体外探索了 PM 暴露后 ROS 诱导的肺损伤。体内研究表明，N-乙酰-L-半胱氨酸（NAC）可以减轻炎症细胞的积累、肺泡壁增厚和肺损伤程度。此外，我们发现 ROS 可以在体内调节细胞内 Ca 水平、瞬时受体电位 Melastatin 2（TRPM2）的表达、NLRP3 及其下游炎症因子。用 A549 细胞和原代 II 型肺泡上皮细胞（SD 细胞）进行的体外实验表明，PM 暴露引起的 ROS 可以通过 TRPM2 介导细胞内 Ca 动员，随后激活 NLRP3。在本研究中，我们证明了 ROS-TRPM2-Ca-NLRP3 途径在 PM 诱导的急性肺损伤中的作用，并为相关病理提供了一个潜在的治疗靶点。
