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.

中文翻译：

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Subway 细颗粒物 （PM2.5） 诱导的促炎反应通过体外 TLRs/NF-κB 依赖性途径触发气道上皮屏障损伤


地铁在全球主要城市得到广泛应用，地铁细颗粒物 （PM2.5） 是城市居民每天 PM2.5 暴露的主要来源。暴露于地铁 PM2.5 会导致人类急性炎症损伤，这已在小鼠体内研究中得到证实。然而，地铁 PM2.5 导致气道损伤的具体机制仍然不清楚。在这项研究中，我们发现地铁 PM2.5 触发了人支气管上皮细胞 （BEAS-2B） 释放促炎细胞因子，如白细胞介素 17E、肿瘤坏死因子 α、转化生长因子 β 和胸腺基质淋巴细胞生成素，呈剂量-效应关系。随后，与地铁 PM2.5 组相比，地铁 PM2.5 组回收的上清液显著增加了 BEAS-2B 细胞中上述细胞因子的表达。此外，地铁 PM2.5 以剂量依赖性方式降低了 BEAS-2B 细胞的紧密连接 （TJ），包括闭合小带-1、E-钙粘蛋白和闭合蛋白。此外，与对照组相比，地铁 PM2.5 组回收的上清液显著降低了这些 TJs 的表达。此外，toll 样受体 （TLR） 和核因子 κB （NF-κB） 的抑制剂，以及螯合物树脂（例如，螯合物）和去铁胺，显着改善了观察到的由 BEAS-2B 细胞中地铁 PM2.5 引起的细胞因子和 TJ 的变化。因此，这些结果表明，地铁 PM2.5 在细胞因子表达最初升高后诱导 TJs 下降，地铁 PM2.5 通过激活 BEAS-2B 细胞中的 TLRs/NF-κB 依赖性通路改变了细胞因子和 TJs 的表达。地铁 PM2.5 的金属成分可能导致气道上皮损伤。