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

IF 4.2 3区 环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES
Aekkacha Moonwiriyakit, Sasiwimol Dinsuwannakol, Jenjira Sontikun, Kanokphorn Timpratueang, Chatchai Muanprasat, Phisit Khemawoot
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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.

细颗粒物PM2.5及其成分六价铬通过炎症体介导的热解作用诱导人气道上皮细胞产生急性细胞毒性。
PM2.5 引发的气道损伤导致呼吸系统发病率上升。然而,人们对PM2.5毒物与急性细胞毒性效应之间的关系仍然知之甚少。本研究旨在探讨PM2.5及其成分诱导人气道上皮细胞细胞毒性的机制。暴露于 PM2.5 会在 24 小时内产生剂量依赖性细胞毒性。在所研究的 PM2.5 成分中,PM2.5 所含剂量的六(Cr)具有细胞毒性作用。PM2.5 和 Cr (VI) 都会导致细胞坏死,同时还会上调促炎细胞因子转录本的表达。有趣的是,暴露于吸附在六(Cr)还原剂 FeSO4 和 EDTA 中的条件 PM 会降低细胞毒性。此外,PM2.5通过激活NLRP3/caspase-1/Gasdermin D途径和增加IL-1β,从机理上增强了程序性脓毒症。当暴露于条件性 PM 时,这些脓毒症标记物会减少。这些发现加深了人们对PM2.5和六(Cr)导致急性气道毒性的机制的理解。
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来源期刊
CiteScore
7.00
自引率
4.70%
发文量
185
审稿时长
34 days
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. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.
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