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

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.

• Authors: 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
• Journal: Journal of environmental sciences (China) (J Environ Sci (China)) Vol. 111 Pg. 429-441 (Jan 2022) ISSN: 1001-0742 [Print] Netherlands
• PMID: 34949371 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier B.V.

Chemical References

• Inflammasomes
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Particulate Matter

Topics

• Air Pollution (adverse effects)
• Cell Line
• Fibrosis
• Humans
• Inflammasomes
• Interleukin-1beta
• Lung
• NLR Family, Pyrin Domain-Containing 3 Protein
• Particulate Matter (toxicity)
• THP-1 Cells