Fine particulate matter PM2.5 and its constituent, hexavalent chromium induce acute cytotoxicity in human airway epithelial cells via inflammasome-mediated pyroptosis

• Published in: Environmental toxicology and pharmacology 2024-04, Vol.107, p.104416-104416, Article 104416
• Main Authors: Moonwiriyakit, Aekkacha, Dinsuwannakol, Sasiwimol, Sontikun, Jenjira, Timpratueang, Kanokphorn, Muanprasat, Chatchai, Khemawoot, Phisit
• Format: Article
• Language: English
• Subjects: Airway epithelial cells; Chromium; Cr(VI); Epithelial Cells; Humans; Inflammasomes - metabolism; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; Particulate Matter - toxicity; PM2.5; Pyroptosis
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/j.etap.2024.104416

PM2.5-induced airway injury contributes to an increased rate of respiratory morbidity. However, the relationship between PM2.5 toxicants and acute cytotoxic effects remains poorly understood. This study aimed to investigate the mechanisms of PM2.5- and its constituent-induced cytotoxicity in human airway epithelial cells. Exposure to PM2.5 resulted in dose-dependent cytotoxicity within 24 h. Among the PM2.5 constituents examined, Cr(VI) at the dose found in PM2.5 exhibited cytotoxic effects. Both PM2.5 and Cr(VI) cause necrosis while also upregulating the expression of proinflammatory cytokine transcripts. Interestingly, exposure to the conditioned PM, obtained from adsorption in the Cr(VI)-reducing agents, FeSO4 and EDTA, showed a decrease in cytotoxicity. Furthermore, PM2.5 mechanistically enhances programmed pyroptosis through the activation of NLRP3/caspase-1/Gasdermin D pathway and increase of IL-1β. These pyroptosis markers were reduced when exposure to conditioned PM. These findings provide a deeper understanding of mechanisms underlying PM2.5 and Cr(VI) in acute airway toxicity. [Display omitted] •PM2.5 induces acute injury and pyroptosis in human airway epithelial cells.•Among substituents in the range of amount found in PM2.5, Cr (VI) causes acute cytotoxicity via necrosis.•Pyroptotic effect of PM2.5 is mitigated by chromium chelators.