Abstract
Fine particulate matter (PM(2.5)) has attracted increasing attention due to its health-threatening effects. Although numerous studies have investigated the impact of PM(2.5) on lung injuries, the specific mechanisms underlying the damage to the air-blood barrier after exposure to PM(2.5) remain unclear. In this study, we established an in vitro co-culture system using lung epithelial cells and capillary endothelial cells. Our findings indicated that the tight junction (TJ) proteins were up-regulated in the co-cultured system compared to the monolayer-cultured cells, suggesting the establishment of a more closely connected in vitro system. Following exposure to PM(2.5), we observed damage to the air-blood barrier in vitro. Concurrently, PM(2.5) exposure induced significant oxidative stress and activated the NLRP3 inflammasome-mediated pyroptosis pathway. When oxidative stress was inhibited, we observed a decrease in pyroptosis and an increase in TJ protein levels. Additionally, disulfiram reversed the adverse effects of PM(2.5), effectively suppressing pyroptosis and ameliorating air-blood barrier dysfunction. Our results indicate that the oxidative stress-pyroptosis pathway plays a critical role in the disruption of the air-blood barrier induced by PM(2.5) exposure. Disulfiram may represent a promising therapeutic option for mitigating PM(2.5)-related lung damage.
