Indoor pollution induced oxinflammatory responses in lung tissues

It has been reported that exposure to indoor PM impairs redox metabolism and promotes inflammation, which might aggravate respiratory diseases. Lung epithelial cells are suggested to play a central role, since they produce inflammatory and oxidative stress mediators following PM uptake. We aimed to study the pathways leading to redox metabolism alterations and NLRP3 inflammasome activation in A549 cells and EpiAlveolar 3D tissue model exposed to Indoor Dust (ID) at the concentration of 25 and 100 μg/mL for up to 24 h. TEM images showed deposits of ID particles inside the cells at 3 and 24 h. In parallel, cells were exposed to ID, showed an increase in intracellular oxidative stress. Moreover, oxidative damage to lipids measured as 4-HNE protein adducts was observed after exposure. Additionally, dose-and time-dependent NFkB nuclear translocation and NLRP3-inflammasome activation was evidenced by the increased IF signal of ASC and NLRP3 after ID exposure. Moreover, an increase in the expression of ASC and NLRP3 was also observed, consistently with an increase in IL-1β levels. Finally, on A549 cells, alteration in wound closure process was observed compared to control. When evaluating EpiAlveolar 3D tissue model exposed to ID an impairment in barrier integrity was found, as indicated by TEER measurement together with an increase in HO-1 and 4-HNE signal. In addition, colocalization of both inflammasome components NLRP3 and ASC, were also found as well as the increased IL-1β levels. Our findings contribute to the understanding of the mechanisms by which ID promotes inflammation and oxidative stress in lung tissues.