PM2.5‐induced pulmonary inflammation via activating of the NLRP3/caspase‐1 signaling pathway

• Published in: Environmental toxicology Vol. 36; no. 3; pp. 298 - 307
• Main Authors: Jia, Hui, Liu, Yang, Guo, Dan, He, Wei, Zhao, Long, Xia, Shuyue
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.03.2021; Wiley Subscription Services, Inc
• Subjects: Air Pollutants - toxicity; Alveoli; Animal models; Animals; Apoptosis; Caspase; Caspase 1 - metabolism; caspase‐1; Cell culture; Cell viability; Cytokines; Cytokines - metabolism; Diseases; Epithelial cells; Epithelial Cells - metabolism; Exposure; Humans; IL‐1β; Inflammasomes - metabolism; Inflammation; Inflammation - chemically induced; Inflammatory diseases; Inflammatory response; Inhalation; Injury prevention; Lung - drug effects; Lung Injury - pathology; Lungs; Mice; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Particulate matter; Particulate Matter - adverse effects; Particulate Matter - toxicity; Pneumonia - chemically induced; Pretreatment; Public concern; pulmonary inflammation; Respiration; Secretion; Signal transduction; Signal Transduction - drug effects; Suspended particulate matter; Therapeutic targets; pulmonary inflammation; particulate matter; NLRP3; IL-1β; caspase-1
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23035

Particulate matter 2.5 (PM2.5)‐induced pulmonary inflammation has become a public concern in recent years. In which, the activation of the NLRP3/caspase‐1 pathway was closely related to the inflammatory response of various diseases. However, the promotion effect of the NLRP3/caspase‐1 pathway on PM2.5‐induced pulmonary inflammation remains largely unclear. Here, our data showed that PM2.5 exposure caused lung injury in the mice by which inflammatory cell infiltration occurred in lung and alveolar structure disorder. Meanwhile, the exposure of human bronchial epithelial cells (16HBE) to PM2.5 resulted in suppressed cell viability, as well as elevated cell apoptosis. Moreover, a higher level of inflammatory cytokine and activation of the NLRP3/caspase‐1 pathway in PM2.5‐induced inflammation mice models and 16HBE cells. Mechanistically, pretreatment with MCC950, a NLRP3/caspase‐1 pathway inhibitor, prevented PM2.5‐induced lung injury, inflammatory response, and the number of inflammatory cells in BALFs, as well as promoted cell viability and decreased inflammatory cytokine secretion. Collectively, our findings indicated that the NLRP3/caspase‐1 pathway serves a vital role in the pathological changes of pulmonary inflammation caused by PM2.5 exposure. MCC950 was expected to be the therapeutic target of PM2.5 inhalation mediated inflammatory diseases.