Selenomethionine mitigate PM2.5-induced cellular senescence in the lung via attenuating inflammatory response mediated by cGAS/STING/NF-κB pathway

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 dis-ease (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-kappa B (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-kappa B pathway activated by DNA damage. Moreover, our study also showed that the pretreatment with seleno-methionine (Se-Met) could inhibit inflammatory response and prevent cellular senescence by hindering cGAS/ STING/NF-kappa B 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 senes-cence in the lung, which provided a novel insight for resisting the harm of PM2.5 to human health.

Automated summary

PM2.5 is a widely known atmospheric pollutant that can induce aging-related pulmonary diseases. This study revealed that PM2.5 induced cellular senescence in the lung through inflammatory response and the cGAS/STING/NF-kappa B pathway activated by DNA damage. The pretreatment with seleno-methionine (Se-Met) inhibited inflammatory response and prevented cellular senescence by hindering this pathway.