The endocrine disruptors nonylphenol and octylphenol exert direct effects on T cells to suppress Th1 development and enhance Th2 development
The endocrine disruptors nonylphenol and octylphenol exert direct effects on T cells to suppress Th1 development and enhance Th2 development
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DOI：
10.1016/j.imlet.2004.04.013
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发表时间：
2004-06-15
影响因子：
4.4
通讯作者：
Miyaura, H
中科院分区：
文献类型：
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作者：
Iwata, M;Eshima, Y;Miyaura, H
一些内分泌干扰物（EDCs）已被证明影响细胞因子的产生和淋巴细胞增殖。然而，内分泌干扰物是否干扰Th 1/Th 2发育尚不清楚。We.选择了广泛用作塑料添加剂和表面活性剂的烷基酚，其中一些被认为是异雌激素。我们研究了它们是否对T细胞产生直接作用以抑制或增强Th 1/Th 2发育。我们使用了两个实验系统与分离的T细胞在体外。在一个系统中，分离的CD 4（+）CD 8（+）胸腺细胞通过两次瞬时刺激和细胞因子处理分化为Th 1和Th 2。在第二个系统中，来自DO11.10 T细胞受体转基因和RAG-2缺陷小鼠的纯化的初始CD 4（+）T细胞通过用细胞因子和针对CD 3和CD 28的抗体处理而分化成Th 1和Th 2。在这两个系统中，1-10 μ M的对-正-壬基酚抑制Th 1的发展和增强Th 2的发展，而雌激素本身不能影响Th 1/Th 2的发展。对正辛基苯酚引起类似的作用，但4-壬基苯酚和对叔辛基苯酚引起弱得多的作用。对正十二烷基酚或对正辛基苯不能影响Th 1/Th 2发育。因此，烷基侧链的长度和支化似乎影响活性。虽然一些烷基酚被认为对视黄酸受体（RAR）或孕酮受体（PRGR）具有弱亲和力，但RAR、PRGR、糖皮质激素受体（GCR）或类维生素A X受体（RXR）的拮抗剂不能抑制活性。这些结果表明，对正壬基苯酚和对正辛基苯酚直接抑制Th 1的发展，并通过独立于雌激素受体，RAR，RXR，PRGR和GCR的机制，促进Th 2的发展。(C)2004 Elsevier B. V.保留所有权利。
Some endocrine disrupting chemicals (EDCs) have been evidenced to affect cytokine production and lymphocyte proliferation. However, it is unknown whether EDCs disturb Th1/Th2 development. We. chose alkylphenols that have been widely used as plastic additives and surfactants, and some of them are recognized as xenoestrogens. We examined whether they exert direct effects on T cells to suppress or enhance Th1/Th2 development. We used two experimental systems with isolated T cells in vitro. In one system, isolated CD4(+)CD8(+) thymocytes differentiated into Th1 and Th2 by two transient stimulations and cytokine treatment. In the second system, purified naive CD4(+) T cells from DO11.10 T cell receptor-transgenic and RAG-2-deficient mice differentiate into Th1 and Th2 by the treatment with cytokines and antibodies to CD3 and CD28. In both systems, 1-10 muM of p-n-nonylphenol suppressed Th1 development and enhanced Th2 development, whereas estrogen by itself failed to affect Th1/Th2 development. p-n-Octylphenol elicited similar effects, but 4-nonylphenol and p-t-octylphenol elicited much weaker effects. p-n-Dodecylphenol or p-n-octylbenzene failed to affect Th1/Th2 development. Thus, the length and branching of the alkyl side chain appeared to affect the activity. Although some alkylphenols have been suggested to have a weak affinity to retinoic acid receptors (RAR) or progesterone receptor (PRGR), antagonists of RAR, PRGR, glucocorticoid receptor (GCR), or retinoid X receptors (RXR) failed to inhibit the activity. These results suggest that p-n-nonylphenol and p-n-octylphenol directly suppress Th1 development and enhance Th2 development through mechanisms independent of estrogen receptors, RAR, RXR, PRGR, and GCR. (C) 2004 Elsevier B.V. All rights reserved.