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.

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

Translational Medical Center,Zhengzhou Central Hospital Affiliated Zhengzhou University,Zhengzhou 450007,China;Division of NanoMedicine,Department of Medicine,University of California,Los Angeles 90095,CA,United States;Basic Medical College,Zhengzhou University,Zhengzhou 450001,China;Department of Ecology and Evolutionary Biology,University of California,Los Angeles 90095,CA,United States;Department of Molecular,Cell and Developmental Biology,University of California,Los Angeles 90095,CA,United States;Department of Integrative Biology and Physiology,University of California,Los Angeles 90095,CA,United States

环境科学学报（英文版）

[1]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-.NLRP3 inflammasome activation determines the fibrogenic potential of PM2.5 air pollution particles in the lung)[J].环境科学学报（英文版）,2022(01):429-441

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