College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, PR China.
Fish Shellfish Immunol. 2011 Apr-May;30(4-5):1131-7. doi: 10.1016/j.fsi.2011.02.020. Epub 2011 Mar 6.
Accumulating evidence suggests that environmental endocrine disrupting chemicals (EDCs) may exert adverse effects on aquatic organisms via the modulation of immune competence in addition to the endocrine system. However, to date, most studies have been undertaken only on biochemical and histopathological endpoints, and few studies have addressed the role of immune response gene transcript abundance in response to estrogen. In the present study, the ontogenetic expression of immune-related genes, including three complement components (C3-1, C3-2 and Bf/C2), two cytokines (IL-21 and type I IFN [IFN]), lysozyme (LZM), novel immune-type receptor (NITR-18), Ikaros (IK) and ceruloplasmin (CP) were characterized during different developmental periods (from 0 to 28 d post-hatch [dph]) in Japanese medaka. Furthermore, the responses of these genes to natural estrogen (i.e., 17β-estradiol [E2]) were evaluated. E2 exposure at sublethal concentrations (0.1-10 μg/L) down-regulated the gene expression of C3-1, C3-2, Bf/C2, LZM and CP, while up-regulating the expression of IL-21, IFN, NITR-18 and IK. The results demonstrate a very different trend in gene expression in fish larvae exposed to E2 when compared with the ontogenetic changes in control, suggesting that exposure to environmental chemicals with estrogenic activities may interfere with immune-related genes and thus potentially influence the susceptibility of fish to opportunistic infections. These findings confirm the ability of exogenous estrogens to elicit changes in immune-related gene expression, and broaden our understanding about the mechanisms underlying the actions of EDCs. In addition, the expression profiles of immune-related genes can be developed for use as biomarkers for future immunotoxicological studies.
越来越多的证据表明,环境内分泌干扰化学物质(EDCs)除了对内分泌系统产生影响外,还可能通过调节免疫能力对水生生物产生不利影响。然而,迄今为止,大多数研究仅在生化和组织病理学终点上进行,很少有研究探讨免疫反应基因转录丰度在雌激素作用下的作用。在本研究中,描述了日本青鳉在不同发育阶段(从孵化后 0 到 28 天[dp h])中免疫相关基因的个体发生表达,包括三个补体成分(C3-1、C3-2 和 Bf/C2)、两种细胞因子(IL-21 和 I 型干扰素[IFN])、溶菌酶(LZM)、新型免疫型受体(NITR-18)、Ikaros(IK)和铜蓝蛋白(CP)。此外,还评估了这些基因对天然雌激素(即 17β-雌二醇[E2])的反应。亚致死浓度(0.1-10μg/L)的 E2 暴露下调了 C3-1、C3-2、Bf/C2、LZM 和 CP 的基因表达,而上调了 IL-21、IFN、NITR-18 和 IK 的表达。与对照相比,鱼幼体暴露于 E2 时基因表达呈现出截然不同的趋势,这表明暴露于具有雌激素活性的环境化学物质可能会干扰免疫相关基因,从而可能影响鱼类对机会性感染的易感性。这些发现证实了外源性雌激素能够引起免疫相关基因表达的变化,并拓宽了我们对 EDC 作用机制的理解。此外,免疫相关基因的表达谱可作为未来免疫毒理学研究的生物标志物。