REGULATION OF THYROID FUNCTION BY TRANSCRIPTION FACTOR NF-kappaB

1. ROI清除系统在甲状腺癌中的作用研究表明，浸润癌细胞的单核细胞分泌具有杀细胞作用的细胞因子。细胞因子的作用是通过产生活性氧中间体（ROI）来实现的。因此，癌细胞中的ROI清除系统可能赋予拮抗细胞因子的细胞毒性作用的能力。在这项研究中，我们研究了编码ROI清除剂，如超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GPX）的mRNA的表达，并将其表达与恶性肿瘤的指标，如淋巴转移。结果表明，有淋巴结转移的甲状腺乳头状癌细胞中锰超氧化物歧化酶mRNA的表达明显增高。铜锌超氧化物歧化酶和GPX的表达与淋巴结转移无关。这些mRNA的表达与肿瘤的局部浸润无关。因此，提示锰的高表达 关于我们 - 乳头状癌细胞中的SOD使其在淋巴转移后存活。FRTL-5大鼠甲状腺细胞NF-κ B活化机制的研究众所周知，TNF-α和IL-6等细胞因子在自身免疫性甲状腺疾病的发生发展中起重要作用。另外已知的事实是，高水平的促甲状腺激素会加重这种疾病。由于细胞因子如TNF-α的作用是通过核因子k B（NF-k B）向细胞核的转运（活化）介导的，因此研究了TSH是否改变TNF-α对NF-k B的活化。当FRTL-5细胞未被TNF-α刺激时，未观察到NF-κ B的活化。当用TNF-α单独刺激细胞时，在细胞核中仅观察到p50-同源二聚体。用TSH和TNF-α联合处理细胞导致细胞核中出现p50-p65异源二聚体。虽然p50是NF-kB的一个亚家族，具有DNA结合活性，但它缺乏激活结构域。因此，p50同源二聚体是转录失活的。另一方面，p65具有DNA结合和激活结构域。我们发现TNF-α诱导p50-p65异源二聚体需要TSH的参与，这表明抑制TSH可能改善自身免疫性甲状腺疾病. TSH介导的对硫氧还蛋白（TRX）和氧化还原因子（Ref-1）的调节最近已经表明，NF-κ B的激活需要被酶如TRX和Ref-1还原。如上所述，TSH调节NF-κ B TNF-α的活化，研究TSH是否调节FRTL-5细胞中TRX和Ref-1的表达。已证明TSH增加TRX和Ref-1两者的表达。少

1. ROLE OF ROI-SCAVENGING SYSTEM IN THYROID CANCERIt has been shown that monocytes infiltrating cancer cells secret cytokines with cytocidal effect. The effect of cytokine is exerted by the production of reactive oxygen intermediates (ROI). It is thus possible that ROI-scavenging system in the cancer cell confer the ability to antagonize the cytotoxic effect of the cytokines. In this study, we investigated the expression of mRNAs coding for ROI-scavengers such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and correlated their expression with indices for malignancies such as lymphatic metastasis. It was revealed that the expression of manganese-SOD mRNA was significantly higher in papillary thyroid cancer cells with lymphatic metastasis. There was no correlation with the expression of Copper-Zinc SOD and GPX with lymphatic metastasis. No correlation was found with local invasion and the expression of these mRNAs. It is thus suggested that the higher expression of manganese … More -SOD in papillary cancer cells renders them to survive after lymphatic metastasis.2. STUDIES ON THE MECHANISM FOR THE ACTIVATION OF NF-kB IN FRTL-5 RAT THYROID CELLSIt is well known that cytokines such as TNF-a and interleukin-6 play important role for the development of autoimmune thyroid disorder. Also known is the fact that high levels of thyroid stimulating hormone aggravate the disorder. Since the effect of cytokines such as TNF-a is mediated through tranlocation of Nuclear factor k B (NF-kB) into the nucleus (activation), it is studied whether TSH modifies the activation of NF-kB by TNF-a. When FRTL-5 cells were not stimulated by TNF-a, no activation of NF-kB was observed. When the cells were stimulated with TNF-a alone, only p50-homodimer was observed in the nuclei. Combined treatment of the cells with TSH and TNF-a resulted in the appearance of p50-p65 heterodimer in the nuclei. Although p50, a subfamily of NF-kB,has DNA-binding activity, it lacks activation domain. Therefore, p50 homodimer is transcriptionally inactive. On the other hand, p65 has both DNA-binding and activation domains. Our finding that induction of p50-p65 heterodimer by TNF-a requires TSH indicates that suppression of TSH in may improve autoimmune thyroid disorder.3. TSH-MEDIATED REGULATION OF THIOREDOXIN (TRX) AND REDOX FACTOR (Ref-1)It has been recently shown that activation of NF-kB requires reduction by the enzymes such as TRX and Ref-1. As mentioned above, TSH modulates the activation of NF-kB TNF-a, it is investigated whether TSH regulates the expression of TRX and Ref-1 in FRTL-5 cells. It was demonstrated that TSH increases the expression of both TRX and Ref-1. Less