Perfluorooctanesulfonate and perfluorooctanoate exacerbate airway inflammation in asthmatic mice and in vitro
Perfluorooctanesulfonate and perfluorooctanoate exacerbate airway inflammation in asthmatic mice and in vitro
复制标题
全氟辛烷磺酸盐和全氟辛酸盐会加剧哮喘小鼠的气道炎症以及体外实验
DOI：
10.1016/j.scitotenv.2020.142365
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发表时间：
2021
影响因子：
9.8
通讯作者：
Li Chun Wei
中科院分区：
文献类型：
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作者：
Yang Mo;Li Li Yue;Qin Xiao Di;Ye Xiao Yan;Yu Shu;Bao Qing;Sun Lin;Wang Zhi Bin;Bloom Michael S.;Jalava Pasi;Hu Li Wen;Yu Hong Yao;Zeng Xiao-Wen;Yang Bo Yi;Dong Guang Hui;Li Chun Wei
新出现的证据表明全氟烷基物质 (PFAS) 暴露与哮喘之间存在关联，但研究结果并不一致。目前的研究旨在调查全氟辛烷磺酸（PFOS）和全氟辛酸盐（PFOA）是否会导致哮喘恶化，并阐明其潜在的生物学机制。目的是a）确定PFOS或PFOA是否会加重小鼠哮喘和肺部炎症；b）研究PFOS和PFOA是否通过JAK-STAT信号通路调节Th1/Th2平衡并加重哮喘。卵清蛋白 (OVA) 诱导的哮喘小鼠通过灌胃暴露于 PFOS 或 PFOA。评估了 PFOS 和 PFOA 血清水平以及器官毒性；还评估了对呼吸道症状、肺组织病理学、辅助性 T 细胞 (Th2) 反应和 STAT6 通路活性的影响。体外 Jurkat 细胞用于研究 PFOS 和 PFOA 介导 Th1 和 Th2 反应的机制。 PFOS 和 PFOA 都会加剧肺组织炎症（嗜酸性粒细胞数量增多和粘液分泌过多），上调 Th2 细胞因子的产生（IL-4 和 IL-13），并促进 Th2 细胞和 STAT6 激活。此外，PFOS 和 PFOA 通过 STAT6 激活增强 Jurkat 细胞的 Th2 反应； Jurkat细胞中STAT6的表达受到抑制后，PFOS暴露对GATA-3、IL-4和IFN-γ的影响被阻断，而PFOA暴露的影响仅被部分阻断。 PFOS和PFOA通过促进淋巴细胞中的Th2反应并通过JAK-STAT信号通路扰乱Th1/Th2的平衡来加重OVA诱导的哮喘小鼠的炎症。
Emerging evidence suggests associations between Perfluoroalkyl substances (PFASs) exposure and asthma, but the findings are inconsistent. The current study sought to investigate whether perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) could contribute to asthma exacerbation and to clarify the underlying biological mechanisms. The objectives are a) to determine whether PFOS or PFOA could aggravate the mouse asthma and pulmonary inflammation b) to investigate whether PFOS and PFOA regulate the balance of Th1/Th2 through the JAK-STAT signaling pathway and aggravated asthma. Ovalbumin (OVA) induced asthmatic mice were exposed to PFOS or PFOA by gavage. PFOS and PFOA serum level and toxicity in organs were assessed; and the impacts on respiratory symptoms, lung tissue pathology, T helper cell (Th2) response, and STAT6 pathway activity were also evaluated. In vitro Jurkat cells were used to study the mechanisms of PFOS and PFOA mediated Th1 and Th2 responses. Both PFOS and PFOA exacerbated lung tissue inflammation (greater number of eosinophils and mucus hyperproduction), upregulated Th2 cytokine production (IL-4 and IL-13), and promoted Th2 cells and STAT6 activation. Furthermore, PFOS and PFOA enhanced the Th2 response in Jurkat cells via STAT6 activation; and the effect of PFOS exposure on GATA-3, IL-4 and IFN-γ was blocked after the expression of STAT6 was suppressed in Jurkat cells, however, the effects of PFOA exposure were only partially blocked. PFOS and PFOA aggravated inflammation among OVA-induced asthmatic mice, by promoting the Th2 response in lymphocytes and disturbing the balance of Th1/Th2 through the JAK-STAT signaling pathway.