Oxidative stress activates the TRPM2-Ca2+-NLRP3 axis to promote PM2.5-induced lung injury of mice - 27/10/20
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Graphical abstract |
Highlights |
• | PM2.5 exposure caused ROS production and inflammatory response. |
• | TRPM2 mediated Ca2+ influx played a vital role in NLRP3 activation. |
• | ROS led to NLRP3 activation after PM2.5-exposure in vivo and in vitro. |
Abstract |
PM2.5, a main particulate air pollutant, poses a serious hazard to human health. The exposure to PM2.5 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 PM2.5-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 PM2.5 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 Ca2+ 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 PM2.5 exposure could mediate intracellular Ca2+ mobilization via TRPM2, with a subsequent activation of NLRP3. In our present study, we demonstrated the contribution of the ROS-TRPM2-Ca2+-NLRP3 pathway in PM2.5-induced acute lung injury and offered a potential therapeutical target valid for related pathology.
Le texte complet de cet article est disponible en PDF.Keywords : PM2.5, Lung injury, ROS, TRPM2, NLRP3
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