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

Abstract

Subways are widely used in major cities around the world, and subway fine particulate matter (PM2.5) is the main source of daily PM2.5 exposure for urban residents. Exposure to subway PM2.5 leads to acute inflammatory damage in humans, which has been confirmed in mouse in vivo studies. However, the concrete mechanism by which subway PM2.5 causes airway damage remains obscure. In this study, we found that subway PM2.5 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 PM2.5 group significantly increased expression of the aforementioned cytokines in BEAS-2B cells compared with the subway PM2.5 group. Additionally, tight junctions (TJs) of BEAS-2B cells including zonula occludens-1, E-cadherin, and occludin were decreased by subway PM2.5 in a dose-dependent manner. Moreover, supernatant recovered from the subway PM2.5 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 PM2.5 in BEAS-2B cells. Therefore, these results suggest that subway PM2.5 induced a decline of TJs after an initial ascent of cytokine expression, and subway PM2.5 altered expression of both cytokines and TJs by activating TLRs/NF-κB-dependent pathway in BEAS-2B cells. The metal components of subway PM2.5 may contribute to the airway epithelial injury.