Caspase-1 Dependent Neutrophil Pyroptosis Contributes to Fine Particulate Matter-Induced Lung Inflammation

As a pollutant, Fine particulate matter (PM2.5) directly deposits in alveoli to induce lung inflammation, yet its pathogenic mechanism remains unclear. PM2.5-induced pulmonary inflammation will trigger the activation of Caspase-1 (Casp1). We seek to elucidate the role of pyroptosis in PM2.5-induced lung inflammation by employing Casp1 knock-out (KO) mice and a specific pyroptosis inhibitor (Disulfiram, DSF). We found the typical pathological changes were comparatively alleviated in the Casp1 KO mice. Notably, in Casp1 KO mice, there was a significant downregulation of gasdermin D (GSDMD) and GSDMD-N at the protein levels. The Casp1 KO mice exhibited a decrease in the numbers of pyroptotic neutrophils. After administrating with DSF, we observed the downregulation of GSDMD and GSDMD-N, along with a decreased number of pyroptotic neutrophils. These findings suggest that neutrophils contribute to PM2.5-induced lung inflammation depending on Caspase-1/pyroptosis signaling pathway. These results demonstrate that PM2.5 triggers lung inflammation via the neutrophil Caspase-1/pyroptosis pathway, revealing a novel mechanism of PM2.5-mediated inflammation and suggesting DSF as a potential therapeutic agent for PM2.5-induced pneumonia.