PM2.5 induces the inflammatory response in rat spleen lymphocytes through autophagy activation of NLRP3 inflammasome

Recent evidence has suggested that fine particulate matter (PM2.5) can induce inflammatory injury in spleen. However, the underlying mechanisms of injury remain enigmatic. In this study, we aim to clarify the inflammatory injury mechanisms of PM2.5 through investigating the crosstalk between autophagy and nod-like receptor protein 3 (NLRP3) inflammasome. The spleen lymphocytes were extracted from SD rats and subjected to PM2.5 and its water-soluble components. The CCK-8 assay was utilized to explore the effects of PM2.5 and its watersoluble components on lymphocytes. Then, the effects of PM2.5 and its water-soluble components exposure on autophagy and NLRP3 inflammasome were detected by qRT-PCR, western blotting, and immunofluorescence staining. The autophagosome production was observed under the transmission electron microscope. The autophagy inhibitor 3-methyladenine (3MA) following PM2.5 water-soluble components was used to investigate the regulation of NLRP3 inflammasome by autophagy. We found that PM2.5 and its water-soluble components decreased the viability of spleen lymphocytes in a dose-dependent manner. PM2.5 exposure and its water-soluble components exposure activated the autophagy and NlRP3 inflammasome, as indicated by an increased expression of LC3, P62, NLRP3, Caspase-1 p10, and increased release of IL-18. Furthermore, the treatment with autophagy inhibitor 3MA attenuated the production of autophagosome and NLRP3 inflammasome induced by PM2.5 water-soluble components with decreased expression of NLRP3, Caspase-1 p10, and diminished production of IL-18. These results suggested that PM2.5 and its water-soluble components could induce autophagy and inflammatory response through NLRP3 inflammasome in spleen lymphocytes, while the NLRP3 inflammasome induced by PM2.5 could be significantly alleviated by inhibition of autophagy, further providing new insights for the understanding of spleen injury caused by PM2.5.