Mechanistic insights into TNF-α and EGF-mediated vascular endothelial activation following PM2.5-induced alveolar injury.

Fine particulate matter (PM2.5), a prevalent air pollutant, reaches pulmonary alveoli and triggers lung inflammation and systemic vascular dysfunction. The alveolar-vascular barrier enables local lung damage to spread to endothelium through soluble factors, making this model fit to analyze lung-systemic interactions. TNF-α and EGF separately dominate inflammatory cascades and endothelial regulation, yet their combined effects during PM2.5 toxicity are unclear. This research constructed a 3D alveolar-vascular barrier model with BEAS-2B, THP-1, and EA. hy926 cells were treated with 0 or 100 μg/mL SRM2786 PM2.5 for 24 h. PM2.5 enters alveolar epithelial cells via endocytosis, causing mitochondrial damage, cell apoptosis, and upregulated TNF-α, EGF, IL-8, TGF-α, and IL-1β. Extracellular TNF-α and EGF cross the barrier and activate the endothelial PI3K-Akt pathway. Increased Nrf2 and CYP1A1 verify progressive oxidative stress. This study illustrates inflammation- and oxidation-dependent crosstalk between alveolar injury and endothelial impairment, clarifying PM2.5 toxic mechanisms and aiding environmental toxicology studies and drug screening.