Misaki T, Takeuchi R, Miyamoto S, Hirano A, Kasagi K, Konishi J
Department of Nuclear Medicine, Kyoto University School of Medicine, Japan.
Clin Exp Immunol. 1994 Nov;98(2):234-9. doi: 10.1111/j.1365-2249.1994.tb06131.x.
In Graves' disease and Hashimoto's thyroiditis, the presence of 72-kD heat shock protein (hsp-72) on thyrocytes has been reported. To clarify the significance of this phenomenon, we induced the antigen in thyroid cell culture in vitro. In the FRTL5 rat cell line, which had been heated at 42.5 degrees C or treated with sodium arsenite, expression of hsp-72 was examined with immunoperoxidase staining and immunoprecipitation of the metabolically labelled protein using a specific MoAb. In the cells cultured either with or without thyrotropin (TSH), heat and chemical stresses reproducibly and dose-dependently induced hsp-72 antigen, whereas unstimulated controls had no significant immunoreactivity. Unlike in Graves' retrocular fibroblasts, hydrogen peroxide was not an effective stress in FRTL5, and the induction was not suppressed by methylmercaptoimmidazole and propylthiouracil, nor enhanced by interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). These data could not support the hypotheses that suppression of thyroid autoimmunity by thionamides is due to their modulatory action on hsp-72 expression, or that presence of that antigen in the thyroid tissues affected by autoimmunity is secondary to cytokine secretion from infiltrating immunocytes. On the other hand, coculture experiments of stressed FRTL5 cells and syngeneic Fisher rat splenocytes suggest that aberrantly expressed hsp may activate part of the thyroid-infiltrating lymphocytes and thereby aggravate autoimmune processes. The induction and detection systems of hsp-72 using FRTL5 cells would facilitate future studies, possibly utilizing human materials as well, to explore possible relations between stress proteins and thyroid autoimmunity.
据报道，在格雷夫斯病和桥本甲状腺炎中，甲状腺细胞上存在72-kD热休克蛋白（hsp-72）。为阐明这一现象的意义，我们在体外甲状腺细胞培养中诱导该抗原。在已在42.5℃加热或用亚砷酸钠处理的FRTL5大鼠细胞系中，使用特异性单克隆抗体通过免疫过氧化物酶染色和代谢标记蛋白的免疫沉淀来检测hsp-72的表达。在有或无促甲状腺激素（TSH）培养的细胞中，热应激和化学应激可重复性地且剂量依赖性地诱导hsp-72抗原，而未受刺激的对照则无明显免疫反应性。与格雷夫斯眼眶后成纤维细胞不同，过氧化氢在FRTL5中不是有效的应激因素，且诱导作用不受甲基巯基咪唑和丙硫氧嘧啶抑制，也不被干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）增强。这些数据不支持以下假说：硫代酰胺对甲状腺自身免疫的抑制作用是由于它们对hsp-72表达的调节作用，或者在受自身免疫影响的甲状腺组织中该抗原的存在继发于浸润免疫细胞的细胞因子分泌。另一方面，应激的FRTL5细胞与同基因Fisher大鼠脾细胞的共培养实验表明，异常表达的hsp可能激活部分甲状腺浸润淋巴细胞，从而加重自身免疫过程。利用FRTL5细胞的hsp-72诱导和检测系统将有助于未来的研究，可能也会利用人类材料，以探索应激蛋白与甲状腺自身免疫之间的可能关系。
