Fine particulate matter-induced lung inflammation is mediated by pyroptosis in mice.

Exposure to ambient air-borne fine particulate matter (PM 2.5) increases respiratory morbidity and mortality. The mechanisms underlying PM 2.5 -induced adverse effects remain unclear. This study aimed to uncover the molecular mechanisms of PM 2.5 -induced lung toxicity using a mouse model. Scanning electron microscopy and inductively coupled plasma mass spectrometry were used to examine and analyze PM 2.5 morphology and element compositions, respectively. Twenty four male mice were randomly divided into three groups: control (PBS), PM 2.5 (4.0 mg/kg b.w.), and PM 2.5 + Z-YVAD-FMK. In the latter group, the pan-caspase inhibitor (Z-YVAD-FMK) was intraperitoneally injected into mice at a dose of 12.5 mg/kg body weight prior to intratracheal instillation of PM 2.5 (4.0 mg/kg b.w.) every other day for a total of 3 times (n = 8 in each group). Bronchoalveolar lavage fluids (BALFs) were collected 24 h after the last instillation of PM 2.5. Levels of total proteins (TP), lactate dehydrogenase (LDH), IL-1β and IL-18 were analyzed for biomarkers of cell injury and inflammation. Additionally, histological alterations of lung tissues were assessed by hematoxylin-eosin staining. mRNA and protein expression of Caspase1, NLRP3 and GSDMD were examined by real-time fluorescent quantitative PCR and immunohistochemical staining. Exposure to PM 2.5 increased levels of TP, LDH, IL-1β, IL-18 and inflammatory cell counts in lung. The mRNA and protein expression of Caspase1, NLRP3 and GSDMD were increased. Inhibition of the NALRP3/Caspase-1 signaling pathway ameliorated PM 2.5 -induced lung injury and inflammation, partially through suppressing pyroptosis in lung. PM 2.5 exposure induces lung injury and inflammation, which is mediated by the NALRP3/Caspase-1 signaling pathway. • PM 2.5 exposure caused lung injury and inflammation in mice. • Inhibition of NALRP3/Caspase-1 signaling pathway can amelioration PM 2.5 -induced lung toxicity. • PM 2.5 exposure induced lung toxicity is related to NALRP3 inflammasome mediated macrophage pyroptosis. [ABSTRACT FROM AUTHOR]