Gallant Melanie J, Hogan Natacha S
Toxicology Graduate Program, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada.
Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada; Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5A8, Canada.
Gen Comp Endocrinol. 2018 Jul 1;263:62-71. doi: 10.1016/j.ygcen.2018.04.008. Epub 2018 Apr 12.
Early life-stages of amphibians rely on the innate immune system for defense against pathogens. While thyroid hormones (TH) are critical for metamorphosis and later development of the adaptive immune system, the role of TH in innate immune system development is less clear. An integral part of the innate immune response are pro-inflammatory cytokines - effector molecules that allow communication between components of the immune system. The objective of this study was to characterize the expression of key pro-inflammatory cytokines, tumor necrosis factor-α (TNFα), interleukin-1β (IL-1β) and interferon-γ (IFN-γ), throughout amphibian development and determine the impacts of thyroidal modulation on their expression. Xenopus laevis were sampled at various stages of development encompassing early embryogenesis to late prometamorphosis and cytokine expression was measured by real-time PCR. Expression of TNFα and IL-1β were transient over development, increasing with developmental stage, while IFN-γ remained relatively stable. Functionally athyroid, premetamorphic tadpoles were exposed to thyroxine (0.5 and 2 μg/L) or sodium perchlorate (125 and 500 μg/L) for seven days. Tadpoles demonstrated characteristic responses of advanced development with thyroxine exposure and delayed development (although to a lesser extent) and increased thyroid gland area and follicular cell height with sodium perchlorate exposure. Exposure to thyroxine for two days resulted in decreased expression of IL-1β in tadpole trunks. Sodium perchlorate had negligible effects on cytokine expression. Overall, these results demonstrate that cytokine transcript levels vary with stage of tadpole development but that their ontogenic regulation is not likely exclusively influenced by thyroid status. Understanding the direct and indirect effects of altered hormone status may provide insight into potential mechanisms of altered immune function during amphibian development.
两栖动物的早期生命阶段依靠先天免疫系统抵御病原体。虽然甲状腺激素（TH）对变态发育和适应性免疫系统的后期发育至关重要，但TH在先天免疫系统发育中的作用尚不清楚。先天免疫反应的一个重要组成部分是促炎细胞因子——这些效应分子使免疫系统各组成部分之间能够相互交流。本研究的目的是描述关键促炎细胞因子肿瘤坏死因子-α（TNFα）、白细胞介素-1β（IL-1β）和干扰素-γ（IFN-γ）在两栖动物整个发育过程中的表达情况，并确定甲状腺调节对其表达的影响。在从早期胚胎发生到前变态晚期的不同发育阶段采集非洲爪蟾样本，通过实时PCR测量细胞因子表达。TNFα和IL-1β的表达在发育过程中是短暂的，随发育阶段增加，而IFN-γ保持相对稳定。功能上甲状腺功能缺失的前变态蝌蚪暴露于甲状腺素（0.5和2μg/L）或高氯酸钠（125和500μg/L）中7天。蝌蚪暴露于甲状腺素后表现出提前发育的特征性反应，暴露于高氯酸钠后发育延迟（尽管程度较轻），甲状腺面积增加，滤泡细胞高度增加。暴露于甲状腺素两天导致蝌蚪躯干中IL-1β的表达降低。高氯酸钠对细胞因子表达的影响可忽略不计。总体而言，这些结果表明细胞因子转录水平随蝌蚪发育阶段而变化，但其个体发育调控不太可能仅受甲状腺状态影响。了解激素状态改变的直接和间接影响可能有助于深入了解两栖动物发育过程中免疫功能改变的潜在机制。
