School of Biology, Food and Environment, Hefei University, Hefei 230601, PR China.
Institute of Agricultural Engineering, Anhui Academy of Agricultural Science, Hefei 230031, PR China.
Ecotoxicol Environ Saf. 2022 Dec 1;247:114266. doi: 10.1016/j.ecoenv.2022.114266. Epub 2022 Nov 2.
Particulate matter 2.5 (PM2.5) is a widely known atmospheric pollutant which can induce the aging-related pulmonary diseases such as acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF). In recent years, with the increasing atmospheric pollution, airborne fine PM2.5, which is an integral part of air pollutants, has become a thorny problem. Hence, this study focused on the effect of PM2.5 on cellular senescence in the lung, identifying which inflammatory pathway mediated PM2.5-induced cellular senescence and how to play a protective role against this issue. Our data suggested that PM2.5 induced time- and concentration-dependent increasement in the senescence of A549 cells. Using an inhibitor of cGAS (PF-06928215) and an inhibitor of NF-κB (BAY 11-7082), it was revealed that PM2.5-induced senescence was regulated by inflammatory response, which was closely related to the cGAS/STING/NF-κB pathway activated by DNA damage. Moreover, our study also showed that the pretreatment with selenomethionine (Se-Met) could inhibit inflammatory response and prevent cellular senescence by hindering cGAS/STING/NF-κB pathway in A549 cells exposed to PM2.5. Furthermore, in vivo C57BL/6J mice model demonstrated that aging of mouse lung tissue caused by PM2.5 was attenuated by decreasing cGAS expression after Se-Met treatment. Our findings indicated that selenium made a defense capability for PM2.5-induced cellular senescence in the lung, which provided a novel insight for resisting the harm of PM2.5 to human health.
细颗粒物 2.5（PM2.5）是一种众所周知的大气污染物，可诱发与衰老相关的肺部疾病，如急性呼吸窘迫综合征（ARDS）、慢性阻塞性肺疾病（COPD）和间质性肺纤维化（IPF）。近年来，随着大气污染的加剧，作为空气污染物的一部分的空气中细颗粒物 PM2.5 已成为一个棘手的问题。因此，本研究专注于 PM2.5 对肺部细胞衰老的影响，确定哪种炎症途径介导了 PM2.5 诱导的细胞衰老，以及如何针对这一问题发挥保护作用。我们的数据表明，PM2.5 诱导 A549 细胞的衰老呈时间和浓度依赖性增加。使用 cGAS 抑制剂（PF-06928215）和 NF-κB 抑制剂（BAY 11-7082），揭示了 PM2.5 诱导的衰老受炎症反应调节，这与 DNA 损伤激活的 cGAS/STING/NF-κB 途径密切相关。此外，我们的研究还表明，用硒代蛋氨酸（Se-Met）预处理可通过抑制 cGAS/STING/NF-κB 途径来抑制炎症反应并防止 A549 细胞暴露于 PM2.5 后发生细胞衰老。此外，体内 C57BL/6J 小鼠模型表明，用 Se-Met 处理后降低 cGAS 表达可减轻 PM2.5 引起的小鼠肺组织衰老。我们的研究结果表明，硒对 PM2.5 诱导的肺部细胞衰老具有防御能力，为抵抗 PM2.5 对人类健康的危害提供了新的见解。
