PDF(Pubmed)
Abstract：
Fine particulate matter (PM2.5) can damage airway epithelial barriers. The anion transport system plays a crucial role in airway epithelial barriers. However, the detrimental effect and mechanism of PM2.5 on the anion transport system are still unclear. In this study, airway epithelial cells and ovalbumin (OVA)-induced asthmatic mice were used. In transwell model, the adenosine triphosphate (ATP)-induced transepithelial anion short-circuit current (Isc) and airway surface liquid (ASL) significantly decreased after PM2.5 exposure. In addition, PM2.5 exposure decreased the expression levels of P2Y2R, CFTR and cytoplasmic free-calcium, but ATP can increase the expressions of these proteins. PM2.5 exposure increased the levels of Th2-related cytokines of bronchoalveolar lavage fluid, lung inflammation, collagen deposition and hyperplasisa of goblet cells. Interestingly, the administration of ATP showed an inhibitory effect on lung inflammation induced by PM2.5. Together, our study reveals that PM2.5 impairs the ATP-induced transepithelial anion Isc through downregulating P2Y2R/CFTR pathway, and this process may participate in aggravating airway hyperresponsiveness and airway inflammation. These findings may provide important insights on PM2.5-mediated airway epithelial injury.
摘要：
细颗粒物(PM2.5)可破坏气道上皮屏障。阴离子转运系统在气道上皮屏障中起着至关重要的作用。然而,PM2.5对阴离子转运系统的有害作用和机制尚不清楚。在这项研究中,使用气道上皮细胞和卵清蛋白（OVA）诱导的哮喘小鼠。在Transwell模型中,暴露于PM2.5后，三磷酸腺苷（ATP）诱导的跨上皮阴离子短路电流（Isc）和气道表面液（ASL）显着降低。此外,PM2.5暴露降低了P2Y2R的表达水平,CFTR和细胞质游离钙，但是ATP可以增加这些蛋白质的表达。PM2.5暴露导致支气管肺泡灌洗液Th2相关细胞因子水平升高,肺部炎症,胶原沉积和杯状细胞增生。有趣的是,给予ATP对PM2.5诱导的肺部炎症有抑制作用。一起,我们的研究表明，PM2.5通过下调P2Y2R/CFTR途径损害ATP诱导的跨上皮阴离子Isc，该过程可能参与加重气道高反应性和气道炎症。这些发现可能为PM2.5介导的气道上皮损伤提供重要见解。
