PM2.5 induces inflammatory responses via oxidative stress-mediated mitophagy in human bronchial epithelial cells

Xuedi Zhai; Jianshu Wang; Jiaojiao Sun; Lili Xin

doi:10.1093/toxres/tfac001

PM_2.5 induces inflammatory responses via oxidative stress-mediated mitophagy in human bronchial epithelial cells

Toxicol Res (Camb). 2022 Jan 19;11(1):195-205. doi: 10.1093/toxres/tfac001. eCollection 2022 Feb.

Authors

Xuedi Zhai¹, Jianshu Wang², Jiaojiao Sun¹, Lili Xin¹

Affiliations

¹ School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, Jiangsu, China.
² Department of Environment Health, Suzhou Center for Disease Prevention and Control, 72 Sanxiang Road, Suzhou 215004, Jiangsu, China.

Abstract

Background: Fine particulate matter (PM_2.5) is a ubiquitous air pollutant, and it has been reported to be closely associated with lung inflammatory injury. In this study, the potential molecular mechanisms underlying PM_2.5-induced cellular inflammation in human bronchial epithelial (BEAS-2B) cells were investigated.

Materials and methods: Ambient PM_2.5 particulates from Suzhou, China, were collected and re-suspended in ultrapure water. Cellular damages, characterized by oxidative stress, mitochondrial injury, and inflammatory cytokine production, were determined in 24 h PM_2.5-treated BEAS-2B cells with or without 3-methyladenine (3-MA; autophagy inhibitor) pretreatment. Biomarkers related to oxidative damage, inflammatory injury and autophagy signaling pathways were also measured.

Results: Uptake of PM_2.5 in BEAS-2B cells induced cellular oxidative damage, mitochondrial injury, and inflammatory responses as indicated by a significant decrease in GSH/GSSG ratio, increased MDA content, dilated mitochondria with loss and rupture of crista, and production of inflammatory cytokines. Activation of Nrf-2/TXNIP-mediated NF-κB and Bnip3L/NIX-dependent mitophagy signaling pathways, as well as accumulation of autophagosomes and autolysosomes, were also observed. A 6 h pretreatment of 3-MA increased PM_2.5-induced oxidative damage and cellular inflammation as indicated by increasing protein levels of HO-1, TXNIP, Bnip3L/NIX and IL-8 gene expression.

Conclusions: PM_2.5 induced cellular inflammatory injury by oxidative stress, mitochondrial dysfunction, and mitophagy initiation. Although induction of Bnip3L/NIX-mediated mitophagy in BEAS-2B cells appeared to confer protection in response to PM_2.5, dysfunction of autophagic flux may be a critical contributor to defective mitophagy and cellular inflammatory response.

Keywords: PM2.5; autophagic flux; inflammation; mitochondrial dysfunction; mitophagy; oxidative stress.