Kotani T, Aratake Y, Ohtaki S
Institute for Clinical Investigation, Miyazaki Medical College Hospital.
Rinsho Byori. 1997 Nov;45(11):1038-47.
It has been suggested that apoptosis plays a pivotal role in the pathogenesis of autoimmune diseases. In Hashimoto's thyroiditis which is a typical organ-specific autoimmune disease, Fas-FasL-mediated apoptosis has been demonstrated as the mechanism of follicular epithelial cell death in which Fas is expressed by IL-1 beta stimulation of FasL is constitutively expressed on follicular epithelial cells. The processes involved in this finding and some questions concerning epithelial cell death are presented. The thyroid tissue of Hashimoto's thyroiditis was examined for DNA fragmentation of follicular epithelial cells by the TUNEL method. DNA fragmentation was observed more frequently on thyroid follicles in the area adjacent to lymphoid cell follicles than on those in the central area. Electron microscopic study supported the results of TUNEL study. Immunohistochemical study on Fas and FasL expression on follicular epithelial cells of various thyroid diseases showed that Fas and FasL were strongly expressed on follicular epithelial cells in Hashimoto's thyroiditis and thyroid cancer. Epithelial cells of patients with Graves' disease and adenomatous goiter, however, were scarcely stained. Fas and FasL expression on follicular epithelial cells were well correlated. In vitro study on follicular epithelial cells clarified that FasL was constitutively expressed on epithelial cells not only in Hashimoto's thyroiditis but also in nontoxic goiter. Fas expression was induced by IL-1 beta stimulation. IL-1 beta stimulation also brought about apoptosis of epithelial cells and epithelial cells killed Fas-positive target cells. Therefore, it was concluded that FasL expressed constitutively on follicular epithelial cells interacts with Fas on epithelial cells expressed by IL-1 beta stimulation to induce apoptosis of epithelial cells.
有人提出，细胞凋亡在自身免疫性疾病的发病机制中起关键作用。在典型的器官特异性自身免疫性疾病桥本甲状腺炎中，Fas - FasL介导的细胞凋亡已被证明是滤泡上皮细胞死亡的机制，其中Fas由白细胞介素 - 1β刺激表达，而FasL在滤泡上皮细胞上组成性表达。本文介绍了这一发现所涉及的过程以及一些关于上皮细胞死亡的问题。通过TUNEL法检测桥本甲状腺炎的甲状腺组织中滤泡上皮细胞的DNA片段化情况。在与淋巴细胞滤泡相邻区域的甲状腺滤泡上比在中央区域的甲状腺滤泡上更频繁地观察到DNA片段化。电子显微镜研究支持了TUNEL研究的结果。对各种甲状腺疾病的滤泡上皮细胞上Fas和FasL表达的免疫组织化学研究表明，Fas和FasL在桥本甲状腺炎和甲状腺癌的滤泡上皮细胞上强烈表达。然而，格雷夫斯病和腺瘤性甲状腺肿患者的上皮细胞几乎没有染色。滤泡上皮细胞上Fas和FasL的表达密切相关。对滤泡上皮细胞的体外研究表明，FasL不仅在桥本甲状腺炎的上皮细胞上组成性表达，而且在非毒性甲状腺肿的上皮细胞上也组成性表达。Fas表达由白细胞介素 - 1β刺激诱导。白细胞介素 - 1β刺激还导致上皮细胞凋亡，并且上皮细胞杀死Fas阳性靶细胞。因此，得出结论，滤泡上皮细胞上组成性表达的FasL与白细胞介素 - 1β刺激所表达的上皮细胞上的Fas相互作用，诱导上皮细胞凋亡。
