Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain.
Dev Comp Immunol. 2012 Mar;36(3):547-56. doi: 10.1016/j.dci.2011.09.011. Epub 2011 Oct 10.
There is increasing public attention concerning the effect of endocrine disruptor chemicals (EDCs) on the immune system. One important group belonging to EDCs are the environmental estrogens. Commonly found in the effluents in wastewater treatment plants, 17α-ethynylestradiol (EE(2)) which is used in contraceptive pills, is an endocrine disruptor with strong estrogenic effects. This study aims to investigate the capacity of EE(2) to modulate in vivo and in vitro the innate immune response of the gilthead seabream (Sparus aurata L.), a teleost species of great commercial value. For this purpose, adult specimens were bath-exposed to EE(2) (0, 5 and 50 ng/L) and then immunized with hemocyanin in the presence of the adjuvant aluminum. The results indicate that, after 15 days of EE(2)-exposure, the disruptor was able to inhibit in a dose-dependent manner the induction of interleukin-1β (IL-1β) gene expression, but did not significantly alter the specific antibody titer. To shed light on the role played by EE(2) into seabream immune response, leukocytes were exposed in vitro to several concentrations of EE(2) (0, 0.5, 5, 50 and 500 ng/ml) for 3, 16 and 48 h and the production of reactive oxygen intermediates, the phagocytic activity and the gene expression profile of these cells were analyzed. EE(2) was seen to inhibit both cellular activities and to alter the immune gene expression profile in primary macrophages. Thus, low concentrations of EE(2) increase the mRNA levels of IL-1 β, IL-6, tumour necrosis factor α and tumour growth factor β in non-activated macrophages. In contrast, EE(2) treatment of activated macrophages resulted in the decreased expression of pro-inflammatory genes and the increased expression of genes encoding anti-inflammatory and tissue remodeling/repair enzymes. Taken together, our results suggest that EE(2) might alter the capacity of fish to appropriately respond to infection although it does not behave as an immunosuppressor.
人们越来越关注内分泌干扰化学物质 (EDCs) 对免疫系统的影响。EDCs 中的一个重要类别是环境雌激素。常用于污水处理厂废水的 17α-乙炔基雌二醇 (EE(2)) 是一种具有强烈雌激素作用的内分泌干扰物，被广泛应用于避孕药中。本研究旨在探究 EE(2) 对真鲷（Sparus aurata L.）固有免疫反应的体内和体外调节能力。真鲷是一种具有重要商业价值的硬骨鱼。为此，成年真鲷经浸浴暴露于 EE(2)（0、5 和 50ng/L），然后在佐剂铝存在的情况下用血蓝蛋白免疫。结果表明，在 EE(2) 暴露 15 天后，该干扰物能够以剂量依赖的方式抑制白细胞介素-1β（IL-1β）基因表达的诱导，但对特异性抗体滴度没有显著影响。为了阐明 EE(2) 对真鲷免疫反应的作用，将白细胞在体外暴露于 EE(2) 的几种浓度（0、0.5、5、50 和 500ng/ml）下 3、16 和 48 小时，分析细胞产生的活性氧中间体、吞噬活性和这些细胞的基因表达谱。EE(2) 被发现既能抑制细胞活性，又能改变原代巨噬细胞的免疫基因表达谱。因此，低浓度的 EE(2) 会增加非激活巨噬细胞中 IL-1β、IL-6、肿瘤坏死因子α和肿瘤生长因子β 的 mRNA 水平。相比之下，EE(2) 处理激活的巨噬细胞会导致促炎基因的表达下调和抗炎和组织重塑/修复酶的表达上调。总之，我们的研究结果表明，EE(2) 可能会改变鱼类对感染的适当反应能力，尽管它本身并不具有免疫抑制作用。
