NLRP3 inflammasome activation and lung fibrosis caused by airborne fine particulate matter

Airborne fine particulate matter (PM2.5) has been known capable of causing lung inflammation and fibrosis, as a result of a series of chronic respiration diseases. Although NLRP3 inflammasome activation is essential for development of many chronic diseases, the relationship between PM2.5-induced toxicological effect and NLRP3 inflammasome activation is rarely investigated. Since PM2.5 contains a large population of nanosized materials and many types of nanomaterials can activate NLRP3 inflammasome, the NLRP3 inflammasome activation and lung fibrosis induced by PM2.5 were investigated in the present study. PM2.5 was found capable of causing weak cell death but potent IL-1β secretion in THP-1 cells, which was involved in NLRP3 inflammasome activation as evidenced by Z-YVAD-FMK inhibited IL-1β secretion and overexpressed ASC and NLRP3 protein in PM2.5 treated cells. PM2.5 could be internalized into cells through multiple endocytosis processes, such as phagocytosis and pinocytosis (macropinocytosis, clathrin- and caveolin-mediated endocytosis), and activate NLRP3 inflammasome through cathepsin B release, ROS production, and potassium efflux. After 21 days of exposure to PM2.5 through oropharyngeal aspiration, Balb/c mice showed increased IL-1β and TGF-β1 levels in the bronchoalveolar lavage fluid (BALF) of lung and significant collagen deposition around small airways of mice, suggesting potential lung inflammation and pulmonary fibrosis.