Fine particulate matter PM2.5 and its constituent, hexavalent chromium induce acute cytotoxicity in human airway epithelial cells via inflammasome-mediated pyroptosis
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引用次数: 0
Abstract
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.
期刊介绍:
Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man.
Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals.
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