Particulate matter (PM) is an environmental pollutant closely associated with human airway inflammation. However, the molecular mechanisms of PM-related airway inflammation remains to be fully elucidated. It is known that COX-2/PGE₂ play key roles in the pathogenesis of airway inflammation. Filaggrin is a transmembrane protein contributing to tight junction barrier function. As such, Filaggrin prevents leakage of transported solutes and is therefore necessary for the maintenance of epithelial integrity. The objective of the present study was to investigate the regulatory mechanisms of COX-2/PGE₂ and Filaggrin upon PM exposure both in vivo and in vitro. C57BL/6 mice received intratracheal instillation of PM for two consecutive days. In parallel, human bronchial epithelial cells (HBECs) were exposed to PM for 24 h. PM exposure resulted in airway inflammation together with upregulation of COX-2/PGE₂ and downregulation of Filaggrin in mouse lungs. Corresponding dysregulation of COX-2/PGE₂ and Filaggrin was also observed in HBECs subjected to PM. PM exposure led to the phosphorylation of ERK, JNK, and PI3K signaling pathways in a time-dependent manner, while blockade of PI3K with the specific molecular inhibitor LY294002 partially reversed the dysregulation of COX-2/PGE₂ and Filaggrin. Moreover, pretreatment of HBECs with NS398, a specific molecular inhibitor of COX-2, and AH6809, a downstream PGE₂ receptor inhibitor, reversed the downregulation of Filaggrin upon PM exposure. Taken together, these data demonstrated that the PI3K signaling pathway upregulated COX-2 as well as PGE₂ and acted as a pivotal mediator in the downregulation of Filaggrin.

中文翻译：

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PI3K信号通路在颗粒物诱导的炎症介质COX-2 / PGE2和支气管上皮中相关的上皮屏障蛋白Filaggrin失调中起关键作用的证据。

颗粒物（PM）是与人类气道炎症密切相关的环境污染物。然而，与PM相关的气道炎症的分子机制仍有待充分阐明。已知COX-2 / PGE ₂在气道炎症的发病机理中起关键作用。膜蛋白是有助于紧密连接屏障功能的跨膜蛋白。因此，聚精蛋白防止运输的溶质泄漏，因此对于维持上皮完整性是必需的。本研究的目的是研究COX-2 / PGE ₂的调控机制体内和体外PM暴露时都含有Filaggrin和Filaggrin。C57BL / 6小鼠连续两天接受气管内PM滴注。同时，将人支气管上皮细胞（HBEC）暴露于PM 24 h。PM暴露导致气道炎症，以及小鼠肺中COX-2 / PGE _2的上调和Filaggrin的下调。在经历过PM的HBEC中也观察到了相应的COX-2 / PGE ₂和Filaggrin失调。PM暴露以时间依赖性方式导致ERK，JNK和PI3K信号通路的磷酸化，而用特异性分子抑制剂LY294002阻断PI3K则部分逆转了COX-2 / PGE ₂的失调。和Filaggrin。此外，用NS398（一种特定的COX-2分子抑制剂）和AH6809（一种下游PGE ₂受体抑制剂）对HBEC进行预处理可逆转PM暴露后丝聚蛋白的下调。综上所述，这些数据表明PI3K信号通路上调了COX-2和PGE ₂并在Filaggrin的下调中起关键作用。