PM2.5 from biofuel smoke induces inflammatory response through the TRPC6/Ca2+/NLRP3 signaling pathway.

Abstract

Household air pollution caused by biomass burning is strongly linked to pulmonary diseases, primarily due to the emission of fine particulate matter (PM_2.5). Pulmonary macrophages, located in the interstitial space and alveolar lumen, are vulnerable to PM_2.5 exposure and play a crucial role in the resulting inflammatory responses. This study investigates the impact of biofuel smoke-derived PM_2.5 (BPM_2.5) on the activation of the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome in macrophages. Short-term exposure to PM_2.5-rich biofuel smoke in rats induced significant pulmonary inflammation, characterized by increased numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid, along with elevated expression of NLRP3 and transient receptor potential channel 6 (TRPC6) in lung tissues. In vitro, BPM_2.5 exposure upregulated the expression of NLRP3 inflammasome components and TRPC6 in macrophages. Notably, knockout of Trpc6 reversed the BPM_2.5-induced increase in NLRP3, ASC, and Caspase 1 expression, decreased intracellular Ca²⁺ concentration ([Ca²⁺]_i), and suppressed the release of pro-inflammatory cytokines IL-1β and IL-18. These findings highlight that BPM_2.5 activates the NLRP3 inflammasome via the TRPC6/Ca²⁺/NLRP3 pathway, contributing to inflammation. This study provides new insights into the molecular mechanisms underlying PM_2.5-induced pulmonary inflammation and suggests potential approaches for the prevention and treatment of PM_2.5-related respiratory diseases.