Selenomethionine mitigate PM2.5-induced senescence of alveolar epithelial cells via attenuating inflammatory response mediated by cGAS/STING/NF-κB pathway

Abstract

Particulate matter 2.5 (PM2.5) is a widely known atmospheric pollutant which could 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 the senescence of pulmonary epithelial (A549) cells, 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 pulmonary epithelial cells. Using a inhibitor of cGAS (PF-06928215) and a 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 when A549 cells were exposed to 100 µg/mL PM2.5 for 48 h, the pretreatment with 20 µM selenomethionine (Se-Met) for 12 h could inhibit inflammatory response and prevent cellular senescence by hindering cGAS/STING/NF-κB pathway. These findings indicated that selenium made a defense capability for PM2.5-induced senescence of alveolar epithelial cells, which provided a novel insight for resisting the harm of PM2.5 to human health.