Experimental autoimmune thyroiditis and/or sialadenitis induced by sodium iodide symporter

碘化钠同向转运蛋白诱导的实验性自身免疫性甲状腺炎和/或唾液腺炎

基本信息

批准号：
13672423
负责人：
HIDAKA Yoh
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

It is not known why about twenty percent of patients with Hashimoto's thyroiditis show the symptoms of Sjogren's syndrome, such as conjunctivitis and xerostomia. Sodium iodide symporter (NIS) expresses not only in thyroid gland but also in salivary gland. The purpose of this study is to examine the pathological role of NIS in autoimmune thyroiditis (Hashimoto's thyroiditis) and autoimmune sialadenitis (Sjogren's syndrome), especially in patients with both diseases. So I plan to examine whether the immunized mice with NIS show thyroiditis and/or sialadenitis or not. CBA/J mice were immunized with NIS expressing 293 cells with TiterMax Gold Adjuvant or Complete Freund's Adjuvant. In some mice, IL-12 was injected with NIS expressing cells to induce Th1 cytokines, which may enhance thyroiditis. Control mice were immunized with NIS non-expressing 293 cells. However the mice immunized with NIS expressing cells did not show lymphocyte infiltration in thyroid gland or salivary gland. Moreover anti-NIS antibody could not be detected in their sera by radioligand assay and iodide-uptake-inhibition assay. I conclude that the immunization with NIS expressing cells could not induce sufficient autoimmune reaction. Recently TSH receptor, which is a membrane protein like NIS, was reported to induce thyroiditis by genetic immunization. I plan to immunize mice with NIS by genetic immunization to induce thyroiditis and sialadenitis.

目前尚不清楚为何约百分之二十的桥本甲状腺炎患者会出现干燥综合征的症状，例如结膜炎和口干症。碘化钠同向转运体（NIS）不仅在甲状腺中表达，也在唾液腺中表达。本研究的目的是探讨 NIS 在自身免疫性甲状腺炎（桥本甲状腺炎）和自身免疫性唾液腺炎（干燥综合征）中的病理作用，特别是在患有这两种疾病的患者中。因此我打算检查NIS免疫小鼠是否表现出甲状腺炎和/或唾液腺炎。使用含有 TiterMax 金佐剂或完全弗氏佐剂的表达 NIS 的 293 细胞对 CBA/J 小鼠进行免疫。在一些小鼠中，IL-12 与 NIS 表达细胞一起注射以诱导 Th1 细胞因子，这可能会加剧甲状腺炎。对照小鼠用不表达NIS的293细胞进行免疫。然而，用NIS表达细胞免疫的小鼠在甲状腺或唾液腺中没有显示淋巴细胞浸润。此外，通过放射性配体测定和碘摄取抑制测定，在他们的血清中无法检测到抗NIS抗体。我的结论是，用NIS表达细胞进行免疫不能诱导足够的自身免疫反应。最近，有报道称TSH受体（一种类似于NIS的膜蛋白）可通过基因免疫诱发甲状腺炎。我计划通过基因免疫的方式用NIS来免疫小鼠，诱发甲状腺炎和唾液腺炎。