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-inflammosome 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 was 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. As outdoor pollutants, it seems oxidative stress and inflammation are the main toxicological mechanism of ID exposure. At the highest dose, ID induces oxidative stress and NLRP3 inflammasome activation leading to IL-1β release in A549 cells. • PM present in domestic environments have similar composition compared to urban air pollution. • PM particles accumulate in the intracellular vesicles and cytoplasm promoting ultrastructural changes in mitochondria and endoplasmic reticulum. • In a similar manner to urban pollution, inflammation and oxidative stress seem to be the main toxicological mechanisms of exposure to indoor pollution. • NLPR3 inflammasome activation is involved in the inflammatory response in lung epithelial cells at highest doses. • In a more realistic model even lowest doses alter the redox metabolism and induce NLRP3 inflammasome activation.