Ndebele Kenneth, Tchounwou Paul B, McMurray Robert W
Molecular Toxicology Research Laboratory, NIH Center for Environmental Health, School of Science and Technology, Jackson State University, Jackson, Mississippi, USA.
Int J Environ Res Public Health. 2004 Mar;1(1):3-11. doi: 10.3390/ijerph2004010003.
Endogenous estrogens are known to modulate several components of immune response, including interleukin-2 (IL-2) production. IL-2 is a cytokine that plays an important role in adaptive immune responses. These responses may be modulated by xenoestrogens such as coumestrol, bisphenol A (BPA), DDT, and TCDD. In this research, we examined the effects and potential mechanisms of action of these estrogenic compounds on IL-2 production in activated CD4+ Jurkat T cells. IL-2 production was analyzed by ELISA and Western Blot. At the transcriptional level, protein expression was examined by RT-PCR. Coumestrol, DDT and TCDD (but not BPA) significantly suppressed IL-2 production in activated CD4+ Jurkat T cells, at the transcriptional and translational levels. The transcriptional suppression of IL-2 was associated with decreased protein levels of NF-kappabeta, an important IL-2 positive transcription factor, without affecting the expression of Ikappa-Balpha protein expression, an important inhibitor of NF-kappabeta nuclear translocation. Although the direct mechanisms of xenoestrogens modulation of the immune system remain to be elucidated, coumestrol-, DDT- and TCDD-induced suppression of IL-2 may have ramifications for our understanding of the impact of xenoestrogens on health and disease.
已知内源性雌激素可调节免疫反应的多个组成部分,包括白细胞介素-2(IL-2)的产生。IL-2是一种在适应性免疫反应中起重要作用的细胞因子。这些反应可能受到异雌激素的调节,如香豆雌酚、双酚A(BPA)、滴滴涕(DDT)和四氯二苯并对二恶英(TCDD)。在本研究中,我们研究了这些雌激素化合物对活化的CD4+ Jurkat T细胞中IL-2产生的影响及其潜在作用机制。通过酶联免疫吸附测定(ELISA)和蛋白质印迹法分析IL-2的产生。在转录水平,通过逆转录聚合酶链反应(RT-PCR)检测蛋白质表达。香豆雌酚、DDT和TCDD(但不包括BPA)在转录和翻译水平上均显著抑制活化的CD4+ Jurkat T细胞中IL-2的产生。IL-2的转录抑制与重要的IL-2阳性转录因子NF-κB蛋白水平降低有关,而不影响NF-κB核转位的重要抑制剂Ikappa-Balpha蛋白的表达。尽管异雌激素调节免疫系统的直接机制仍有待阐明,但香豆雌酚、DDT和TCDD诱导的IL-2抑制可能会影响我们对异雌激素对健康和疾病影响的理解。