Airborne fine particulate matter (PM2.5) is known to cause respiratory inflammation such as chronic obstructive pulmonary disease and lung fibrosis.NLRP3 inflammasome acti-vation has been implicated in these diseases;however,due to the complexity in PM2.5 compositions,it is difficult to differentiate the roles of the components in triggering this pathway.We collected eight real-life PM2.5 samples for a comparative analysis of their ef-fects on NLRP3 inflammasome activation and lung fibrosis.In vitro assays showed that al-though the PM2.5 particles did not induce significant cytotoxicity at the dose range of 12.5 to 100 μg/mL,they induced potent TNF-α and IL-1β production in PMA differentiated THP-1 human macrophages and TGF-β1 production in BEAS-2B human bronchial epithelial cells.At the dose of 100 lμg/mL,PM2.5 induced NLRP3 inflammasome activation by inducing lyso-somal damage and cathepsin B release,leading to IL-1β production.This was confirmed by using NLRP3-and ASC-deficient cells as well as a cathepsin B inhibitor,ca-074 ME.Ad-ministration of PM2.5 via oropharyngeal aspiration at 2 mg/kg induced significant TGF-β1 production in the bronchoalveolar lavage fluid and collagen deposition in the lung at 21 days post-exposure,suggesting PM2.5 has the potential to induce pulmonary fibrosis.The ranking of in vitro IL-1β production correlates well with the in vivo total cell count,TGF-β1 production,and collagen deposition.In summary,we demonstrate that the PM2.5 is capable of inducing NLRP3 inflammasome activation,which triggers a series of cellular responses in the lung to induce fibrosis.