Tian Xiaoli, Takamoto Masaya, Sugane Kazuo
Department of Immunology and Infectious Diseases, Institute of Organ Tansplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Int Arch Allergy Immunol. 2003 Nov;132(3):240-7. doi: 10.1159/000074305.
It has been proposed that estrogen plays an important role in modulating the Th1/Th2 cytokine balance. From this viewpoint, chemicals with estrogenic responses were expected to possess similar immunoregulatory roles which have not been defined to date. To address this, we studied the effects of one of the estrogenic chemicals, bisphenol A (BPA), on the in vitro production of Th1 and Th2 cytokines.
Mesenteric lymph node cells from Trichinella spiralis (Ts)-infected mice were incubated with serialfold dilutions of BPA under stimulation with Ts antigen. The Th2 cytokine production in the supernatant was determined by ELISA. The Th2 cytokine production by mesenteric lymph node cells from Ts-infected mice inoculated orally with BPA was compared with that of uninoculated mice infected with Ts.
The antigen-stimulated interleukin (IL)-4 production by Th2-dominant mesenteric lymph node cells from Ts-infected mice increased significantly by addition of 3 microM of BPA. The IL-5 production was not affected. The production of IL-4, but not that of IL-5, by splenocytes of Th2-skewed Leishmania major-infected BALB/c mice increased at concentrations of 3 and 10 microM of BPA. However, the interferon gamma production was not affected by BPA in Th1-skewed L. major-infected C57BL/6 mice. The production of IL-4 and IL-10, but not that of IL-13, markedly increased in Ts-infected mice inoculated orally with BPA.
We demonstrated that the IL-4 production was increased both in vitro and in vivo by treatment with BPA. This suggests that BPA might cause allergic diseases by stimulating the IL-4 production by Th2 cells.
有人提出雌激素在调节Th1/Th2细胞因子平衡中起重要作用。从这一观点来看，具有雌激素反应的化学物质有望具有类似的免疫调节作用，而迄今为止尚未明确。为解决这一问题，我们研究了一种具有雌激素作用的化学物质双酚A（BPA）对Th1和Th2细胞因子体外产生的影响。
将旋毛虫（Ts）感染小鼠的肠系膜淋巴结细胞与系列稀释的BPA在Ts抗原刺激下孵育。通过酶联免疫吸附测定法（ELISA）测定上清液中Th2细胞因子的产生。将经口接种BPA的Ts感染小鼠的肠系膜淋巴结细胞产生的Th2细胞因子与未接种的Ts感染小鼠进行比较。
添加3 microM的BPA后，Ts感染小鼠中以Th2为主的肠系膜淋巴结细胞经抗原刺激产生的白细胞介素（IL）-4显著增加。IL-5的产生不受影响。在浓度为3和10 microM的BPA作用下，偏向Th2的利什曼原虫主要感染的BALB/c小鼠脾细胞产生的IL-4增加，但IL-5的产生不受影响。然而，在偏向Th1的利什曼原虫主要感染的C57BL/6小鼠中，干扰素γ的产生不受BPA影响。经口接种BPA的Ts感染小鼠中，IL-4和IL-10的产生显著增加，但IL-13的产生未增加。
我们证明，用BPA处理在体外和体内均增加了IL-4的产生。这表明BPA可能通过刺激Th2细胞产生IL-4而导致过敏性疾病。
