Background
Fine particulate matter (PM2.5) 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 PM2.5-induced cellular inflammation in human bronchial epithelial (BEAS-2B) cells were investigated. Materials and
Conclusions
PM2.5 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 PM2.5, dysfunction of autophagic flux may be a critical contributor to defective mitophagy and cellular inflammatory response.
Methods
Ambient PM2.5 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 PM2.5-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 PM2.5 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 PM2.5-induced oxidative damage and cellular inflammation as indicated by increasing protein levels of HO-1, TXNIP, Bnip3L/NIX and IL-8 gene expression. Conclusions: PM2.5 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 PM2.5, dysfunction of autophagic flux may be a critical contributor to defective mitophagy and cellular inflammatory response.