Effect of acute PM2.5 exposure on PTGS2 and RNA m6A modification

Particulate matter 2.5 (PM2.5) is a prevalent risk factor in many diseases, but its molecular mechanism remains ambiguous and may be diverse. RNA m6A is an important epigenetic modification that regulates gene expression at the post-transcriptional level. Some previous animal exposure studies found that PM2.5 exposure up-regulated m6A RNA methylation in the lung, but there is no research on m6A RNA methylation in humans from PM2.5 exposure now. Here, in the present experiment, we performed a panel study of 65 students at the Chinese research academy of environmental sciences (CRAES) with 3 rounds of follow-up visits from August 2021 to January 2022. We examined m6A RNA modification profiles of peripheral blood mononuclear cells (PBMCs) from subjects after low and high concentrations of ambient PM2.5 exposure. We applied a linear mixed-effect (LME) model to investigate the association between PM2.5 exposure and global m6A RNA methylation and PTGS2 level in peripheral blood. We found that increased levels of global m6A RNA methylation and PTGS2 level were associated with higher PM2.5 exposure. Among the methylated mRNAs, PTGS2 was hyper-methylated after high concentrations of PM2.5 exposure, which coincided with the increased expression of PTGS2 mRNA. In the present study, we determined that PM2.5 exposure promoted RNA m6A modification, and PTGS2 in peripheral blood could serve as a novel regulatory factor of inflammation induced by PM2.5 exposure. Furthermore, RNA m6A modification may contribute to the altered expression of PTGS2 induced by PM2.5 exposure. Our finding provided a new perspective for the prevention and treatment of PM2.5 exposure-induced adverse health effects.