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

Linlin Guan; Hao Shi; Jiayu Tian; Xin Wang; Nannan Liu; Caihong Wang; Zhihong Zhang

doi:10.1016/j.molimm.2023.07.009

PM_2.5 induces the inflammatory response in rat spleen lymphocytes through autophagy activation of NLRP3 inflammasome

Mol Immunol. 2023 Sep:161:74-81. doi: 10.1016/j.molimm.2023.07.009. Epub 2023 Jul 27.

Authors

Linlin Guan¹, Hao Shi², Jiayu Tian³, Xin Wang³, Nannan Liu³, Caihong Wang³, Zhihong Zhang⁴

Affiliations

¹ Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, China; Yellow River Basin Ecological Public Health Security Center, Shanxi Medical University, Taiyuan, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China; Department of Clinical Laboratory, Shanxi Provincial People's Hospital,Taiyuan, China.
² Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, China; Yellow River Basin Ecological Public Health Security Center, Shanxi Medical University, Taiyuan, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China; Department of public health, Linyi Cancer Hospital, Linyi, China.
³ Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, China; Yellow River Basin Ecological Public Health Security Center, Shanxi Medical University, Taiyuan, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China.
⁴ Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, China; Yellow River Basin Ecological Public Health Security Center, Shanxi Medical University, Taiyuan, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China. Electronic address: zzh1973@sxmu.edu.cn.

PMID: 37506549
DOI: 10.1016/j.molimm.2023.07.009

Abstract

Recent evidence has suggested that fine particulate matter (PM_2.5) 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 PM_2.5 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 PM_2.5 and its water-soluble components. The CCK-8 assay was utilized to explore the effects of PM_2.5 and its water-soluble components on lymphocytes. Then, the effects of PM_2.5 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 PM_2.5 water-soluble components was used to investigate the regulation of NLRP3 inflammasome by autophagy. We found that PM_2.5 and its water-soluble components decreased the viability of spleen lymphocytes in a dose-dependent manner. PM_2.5 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-1β. Furthermore, the treatment with autophagy inhibitor 3MA attenuated the production of autophagosome and NLRP3 inflammasome induced by PM_2.5 water-soluble components with decreased expression of NLRP3, Caspase-1 p10, and diminished production of IL-1β. These results suggested that PM_2.5 and its water-soluble components could induce autophagy and inflammatory response through NLRP3 inflammasome in spleen lymphocytes, while the NLRP3 inflammasome induced by PM_2.5 could be significantly alleviated by inhibition of autophagy, further providing new insights for the understanding of spleen injury caused by PM_2.5.

Keywords: Autophagy; NLRP3 inflammasome; PM(2.5); Spleen lymphocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy
Caspase 1 / metabolism
Inflammasomes* / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
NLR Proteins
Particulate Matter / toxicity
Rats
Rats, Sprague-Dawley
Spleen / metabolism

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
NLR Proteins
Caspase 1
Particulate Matter