The sodium iodide symporter gene and its regulation by cytokines found in autoimmmunity

The sodium iodide symporter gene and its regulation by cytokines found in autoimmmunity
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DOI:
10.1677/joe.0.1580351
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发表时间:
1998-09-01
影响因子:
4
通讯作者:
Weetman, AP
Weetman, AP
中科院分区:
医学2区
文献类型:
--
作者:
Ajjan, RA;Watson, PF;Weetman, AP

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甲状腺的碘浓度是甲状腺激素合成的重要步骤,由Na+/I-转运体(NIS)介导。为了确定可能调控这一过程的因素,我们用半定量逆转录-聚合酶链式反应(RT-PCR)技术研究了NIS基因在Fisher大鼠甲状腺细胞系(FRTL-5)中的表达。将不同浓度的牛TSH(0.1、1、10、50和100mU/l)分别加入FRTL-5细胞中,加入或不加入肿瘤坏死因子-α(TNF-α)、干扰素-γ(干扰素-γ)或白介素1-α(IL-1α),至少5天。提取RNA,对样品进行NIS表达研究。TSH以剂量依赖的方式促进NIS mRNA的表达,在0-1mU/l时诱导明显,在50mU/l时达到高峰,刺激6h后即可检测到这种作用,但在刺激后2 h内无此作用,而TNFα和IL-1α对基础和TSH诱导的NIS表达均有抑制作用。高浓度的干扰素也下调了TSH刺激的NIS mRNA的表达。使用相同的技术,我们还研究了NIS mRNA在两只雄性和一只雌性Wistar大鼠中的组织分布。NIS在甲状腺、胃和乳腺中表达较高,在肠、脂肪组织和肝脏中表达较低,在唾液腺中表达较低,在肾脏中未见表达。综上所述,TSH在体外上调了大鼠NIS基因的表达,这种诱导可以被细胞因子调节。体外分析大鼠NIS mRNA的分布表明,不同组织样本中NIS转录水平不同。
Iodide concentration by the thyroid gland, an essential step for thyroid hormone synthesis, is mediated by the Na+/I- symporter (NIS). To identify factors that may regulate this process, we have studied NIS gene expression in the Fisher rat thyroid cell line (FRTL-5) by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. Increasing concentrations of bovine TSH (0.1, 1, 10, 50 and 100 mU/1), with or without tumour necrosis factor-alpha (TNF alpha), interferon-gamma (IFN gamma) or interleukin-1 alpha (IL-1 alpha) were added to FRTL-5 cells previously deprived of TSH for a minimum of 5 days. RNA was extracted and samples were studied for NIS expression. TSH enhanced NIS mRNA expression in a dose-dependent manner, with induction evident at 0-1 mU/1, reaching a peak at 50 mU/1, an effect detected after 6 h of stimulation, but not in the first 2 h. Both TNF alpha and, to a lesser extent, IL-1 alpha inhibited basal and TSH-induced NIS expression. High concentrations of IFN gamma also downregulated TSH-stimulated NIS mRNA expression.Using the same technique, we also investigated NIS mRNA tissue distribution in two male and one female Wistar rats. High levels of NIS expression were detected in the thyroid, stomach, and mammary gland, lower levels were found in the intestine, adipose tissue and liver, borderline levels were expressed in the salivary gland, and no expression was detected in the kidneys.In summary, we have shown that TSH upregulates rat NIS gene expression in vitro, and this induction can be modulated by cytokines. Analysis of the distribution of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcription in different tissue samples.