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NLRP3 inflammasome activation determines the fibrogenic potential of PM2.5 air pollution particles in the lung

Author:
Wei Cao, Xiang Wang, Jiulong Li, Ming Yan, Chong Hyun Chang, Joshua Kim, Jinhong Jiang, Yu-Pei Liao, Shannon Tseng, Sydney Kusumoputro, Candice Lau, Marissa Huang, Pengli Han, Pengju Lu, Tian Xia
Source:
Journal of environmental sciences (China) 2022 v.111 pp. 429-441
ISSN:
1001-0742
Subject:
air pollution, cathepsin B, collagen, cytotoxicity, epithelium, fibrosis, humans, inflammasomes, inflammation, lungs, macrophages, particulates, pulmonary fibrosis, China
Abstract:
Airborne fine particulate matter (PM₂.₅) is known to cause respiratory inflammation such as chronic obstructive pulmonary disease and lung fibrosis. NLRP3 inflammasome activation 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 effects on NLRP3 inflammasome activation and lung fibrosis. In vitro assays showed that although 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 µg/mL, PM₂.₅ induced NLRP3 inflammasome activation by inducing lysosomal 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. Administration 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.
Agid:
7377867