PM2.5 engages impairment of mucosal immunity, involving alteration of complement activation and cell junction assembly by regulated IL-17 levels: Pathological and proteomic approaches

Fine particulate matter (PM2.5) exacerbates respiratory morbidity, posing significant health and environmental concerns. Although PM2.5 causes various adverse effects on the respiratory tract, the mechanisms of PM2.5-induced lung toxicity have been incompletely characterized. Thus, this study aims to investigate the mechanisms of PM2.5-induced lung inflammation. BALB/c mice were intratracheally administered with concentrations of PM2.5 daily for 7 days. Histopathological analyses of lung tissue were performed. Bronchoalveolar lavage fluid proteomics was analyzed using QTOF LC-MS/MS, and differentially expressed genes were visualized through volcano plots and heatmaps. Functional protein data were further assessed by GO enrichment analysis, KEGG pathways, and STRING protein networking. Moreover, specific proteins of interest were validated using multiplex ELISA. We found that PM2.5 induced marked neutrophilic inflammation in the lungs, as evidenced by the increase of polymorphonuclear cells and macrophages in a dose-dependent manner. Proteomics analysis identified 147 differentially expressed proteins, with 43 down-regulated and 104 up-regulated. Gene ontology analysis revealed that up-regulated proteins are mainly secretory and implicated in the inflammatory response, complement activation, and assembly of various cell junctions. Additionally, a decrease in serum IL-17A levels, supported by STRING network analysis, suggests its involvement in PM2.5-induced mucosal immunity impairment in the respiratory tract and potentially in non-exposed organs. These findings provide mechanistic insight into PM2.5-induced inflammation, facilitating the development of biomarkers of PM2.5 exposure and targeted therapies for PM2.5-related lung diseases.