Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan.
J Appl Toxicol. 2013 Dec;33(12):1451-9. doi: 10.1002/jat.2809. Epub 2012 Sep 12.
Brominated flame retardants (BFRs) are widely used in consumer products. Their toxicological effects as endocrine disruptors have been partly examined. However, their immunological effects have not been elucidated. To evaluate the effects of BFRs on immune responses, we investigated whether BFRs affect phenotypes and the function of immune cells in vitro. Here we examined the commercial pentabromodiphenyl ether mixture (DE-71), octabromodiphenyl ether mixture (DE-79), decabromodiphenyl ether mixture (DE-83R), hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA). Splenocytes and bone marrow (BM) cells were prepared from atopic prone NC/Nga mice. Splenocytes were exposed to each BFR for 24 h. BM cells were cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) for 8 days and BM-derived dendritic cells (BMDCs) were exposed to each BFR for 24 h. In another experiment, BM cells were cultured with GM-CSF in the presence of each BFR for 6 days during BMDC differentiation. After exposure, cell surface molecule expression and cytokine production were investigated. Each BFR increased MHC class II and CD86 expression and interleukin (IL)-4 production in splenocytes. DE-71, HBCD and TBBPA increased T cell receptor (TCR) expression in splenocytes. In both experiments, all BFRs except TBBPA increased DEC205 expression in BMDCs. BMDCs that differentiated in the presence of HBCD showed enhanced MHC class II, CD80, CD86 and CD11c expression. The results demonstrate that some BFRs may stimulate immune cells. BFRs can induce or enhance immune/allergic responses by increasing antigen presentation-related molecule expression and IL-4 production.
溴系阻燃剂（BFRs）广泛应用于消费品中。它们作为内分泌干扰物的毒理学效应已部分得到研究。然而，它们的免疫学效应尚未阐明。为了评估 BFRs 对免疫反应的影响，我们研究了 BFRs 是否会影响体外免疫细胞的表型和功能。在这里，我们研究了商用五溴二苯醚混合物（DE-71）、八溴二苯醚混合物（DE-79）、十溴二苯醚混合物（DE-83R）、六溴环十二烷（HBCD）和四溴双酚 A（TBBPA）。从特应性倾向的 NC/Nga 小鼠中制备脾细胞和骨髓（BM）细胞。将脾细胞暴露于每种 BFR 中 24 小时。将 BM 细胞用粒细胞-巨噬细胞集落刺激因子（GM-CSF）培养 8 天，并将 BM 来源的树突状细胞（BMDC）暴露于每种 BFR 中 24 小时。在另一个实验中，在 BMDC 分化期间，将 BM 细胞与 GM-CSF 一起在每种 BFR 存在的情况下培养 6 天。暴露后，研究细胞表面分子表达和细胞因子产生情况。每种 BFR 均增加脾细胞中 MHC Ⅱ类和 CD86 的表达和白细胞介素（IL）-4 的产生。DE-71、HBCD 和 TBBPA 增加了脾细胞中的 TCR 表达。在这两个实验中，除 TBBPA 外，所有 BFR 均增加了 BMDC 中的 DEC205 表达。在 HBCD 存在下分化的 BMDC 显示出增强的 MHC Ⅱ类、CD80、CD86 和 CD11c 的表达。结果表明，一些 BFR 可能会刺激免疫细胞。BFR 可以通过增加抗原呈递相关分子的表达和 IL-4 的产生来诱导或增强免疫/过敏反应。
