Subway Fine Particles (PM2.5)-Induced Pro-Inflammatory Response Triggers Airway Epithelial Barrier Damage Through the TLRs/NF-κB-Dependent Pathway In Vitro

Subways are widely used in major cities around the world, and subway fine particulate matter (PM_2.5) is the main source of daily PM_2.5 exposure for urban residents. Exposure to subway PM_2.5 leads to acute inflammatory damage in humans, which has been confirmed in mouse in vivo studies. However, the concrete mechanism by which subway PM_2.5 causes airway damage remains obscure. In this study, we found that subway PM_2.5 triggered release of pro-inflammatory cytokines such as interleukin 17E, tumor necrosis factor α, transforming growth factor β, and thymic stromal lymphopoietin from human bronchial epithelial cells (BEAS-2B) in a dose–effect relationship. Subsequently, supernatant recovered from the subway PM_2.5 group significantly increased expression of the aforementioned cytokines in BEAS-2B cells compared with the subway PM_2.5 group. Additionally, tight junctions (TJs) of BEAS-2B cells including zonula occludens-1, E-cadherin, and occludin were decreased by subway PM_2.5 in a dose-dependent manner. Moreover, supernatant recovered from the subway PM_2.5 group markedly decreased the expression of these TJs compared with the control group. Furthermore, inhibitors of toll-like receptors (TLRs) and nuclear factor-kappa B (NF-κB), as well as chelate resins (e.g., chelex) and deferoxamine, remarkably ameliorated the observed changes of cytokines and TJs caused by subway PM_2.5 in BEAS-2B cells. Therefore, these results suggest that subway PM_2.5 induced a decline of TJs after an initial ascent of cytokine expression, and subway PM_2.5 altered expression of both cytokines and TJs by activating TLRs/NF-κB-dependent pathway in BEAS-2B cells. The metal components of subway PM_2.5 may contribute to the airway epithelial injury.