急性低剂量暴露于成年雄性小鼠的氯化阻燃剂Dechlorane 602以及Th1和Th2免疫反应的影响。,Environmental Health Perspectives - X-MOL

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急性低剂量暴露于成年雄性小鼠的氯化阻燃剂Dechlorane 602以及Th1和Th2免疫反应的影响。
Environmental Health Perspectives ( IF 10.1 ) Pub Date : 2016-04-16 , DOI: 10.1289/ehp.1510314
Yu Feng ₁ , Jijing Tian , Heidi Qunhui Xie , Jianwen She , Sherry Li Xu , Tuan Xu , Wenjing Tian , Hualing Fu , Shuaizhang Li , Wuqun Tao , Lingyun Wang , Yangsheng Chen , Songyan Zhang , Wanglong Zhang , Tai L Guo , Bin Zhao

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背景技术尽管已经在食物，人血液和母乳中检测到氯化阻燃剂十氯烷（Dec）602，但是有关潜在健康影响（包括可能的免疫毒性）的信息有限。目的我们通过检查胸腺细胞和脾淋巴细胞亚群上的表型标志物的表达，Th1 / Th2转录因子以及细胞因子和抗体的产生，确定了Dec 602在小鼠中的免疫毒性潜力。方法成年雄性C57BL / 6小鼠连续7天口服与环境相关剂量的Dec 602（每天1和10μg/ kg体重）。通过流式细胞术分析胸腺细胞和脾脏CD4和CD8子集以及脾细胞凋亡。在mRNA和蛋白质水平都测量了细胞因子的表达。使用定量实时聚合酶链反应（qPCR）确定转录因子Th1（T-bet和STAT1）和Th2（GATA3）的水平。血清免疫球蛋白IgG1，IgG2a，IgG2b和IgE的水平通过酶联免疫吸附法（ELISA）进行测定。结果与溶媒对照组相比，脾脏CD4 +和CD8 + T细胞亚群减少，而脾脏CD4 + T细胞凋亡明显增加。Th2细胞因子[白介素（IL）-4，IL-10和IL-13]的表达（mRNA和蛋白）增加，Th1细胞因子[IL-2，干扰素（IFN）-γ和肿瘤坏死因子（TNF）的表达增加）-α]降低。Th2转录因子GATA3增加，而Th1转录因子T-bet和STAT1减少。作为Th2-Th1失衡的其他指标，IgG1的产生显着增加，而IgG2a降低了。结论据我们所知，我们是第一个报告Dec 602对小鼠免疫功能的影响的证据，发现表明Dec 602暴露有利于Th2反应并降低Th1功能。引文冯Y，田静，谢总部，佘健，徐士林，徐婷，田威，傅海，李升，陶望，王力，陈怡，张胜，张望，郭天乐，赵斌.2016急性小剂量暴露于成年雄性小鼠的氯化阻燃剂十氯烷602和Th1和Th2免疫反应的影响。Environ Health Perspect 124：1406-1413；http://dx.doi.org/10.1289/ehp.1510314。佘健，徐圣林，徐天，田威，付红，李升，陶威，王力，陈毅，张胜，张伟，郭德良，赵本。2016。急性低剂量暴露对糖尿病的影响。氯化阻燃剂十氯烷602和成年雄性小鼠的Th1和Th2免疫反应。Environ Health Perspect 124：1406-1413；http://dx.doi.org/10.1289/ehp.1510314。佘健，徐圣林，徐天，田威，付红，李升，陶威，王力，陈毅，张胜，张伟，郭德良，赵本。2016。急性低剂量暴露对糖尿病的影响。氯化阻燃剂十氯烷602和成年雄性小鼠的Th1和Th2免疫反应。Environ Health Perspect 124：1406-1413；http://dx.doi.org/10.1289/ehp.1510314。

"点击查看英文标题和摘要"

Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice.

BACKGROUND Although the chlorinated flame retardant Dechlorane (Dec) 602 has been detected in food, human blood, and breast milk, there is limited information on potential health effects, including possible immunotoxicity. OBJECTIVES We determined the immunotoxic potential of Dec 602 in mice by examining the expression of phenotypic markers on thymocyte and splenic lymphocyte subsets, Th1/Th2 transcription factors, and the production of cytokines and antibodies. METHODS Adult male C57BL/6 mice were orally exposed to environmentally relevant doses of Dec 602 (1 and 10 μg/kg body weight per day) for 7 consecutive days. Thymocyte and splenic CD4 and CD8 subsets and splenocyte apoptosis were examined by flow cytometric analysis. Cytokine expression was measured at both the mRNA and the protein levels. Levels of the transcription factors Th1 (T-bet and STAT1) and Th2 (GATA3) were determined using quantitative real-time polymerase chain reaction (qPCR). Serum levels of immunoglobulins IgG1, IgG2a, IgG2b and IgE were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Splenic CD4+ and CD8+ T cell subsets were decreased compared with vehicle controls, and apoptosis was significantly increased in splenic CD4+ T cells. Expression (mRNA and protein) of Th2 cytokines [interleukin (IL)-4, IL-10, and IL-13] increased, and that of Th1 cytokines [IL-2, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] decreased. The Th2 transcriptional factor GATA3 increased, whereas the Th1 transcriptional factors T-bet and STAT1 decreased. As additional indicators of the Th2-Th1 imbalance, production of IgG1 was significantly increased, whereas IgG2a was reduced. CONCLUSIONS To our knowledge, we are the first to report evidence of the effects of Dec 602 on immune function in mice, with findings indicating that Dec 602 exposure favored Th2 responses and reduced Th1 function. CITATION Feng Y, Tian J, Xie HQ, She J, Xu SL, Xu T, Tian W, Fu H, Li S, Tao W, Wang L, Chen Y, Zhang S, Zhang W, Guo TL, Zhao B. 2016. Effects of acute low-dose exposure to the chlorinated flame retardant dechlorane 602 and Th1 and Th2 immune responses in adult male mice. Environ Health Perspect 124:1406-1413; http://dx.doi.org/10.1289/ehp.1510314.

更新日期：2019-11-01

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