Xiao Wen-hua, Hong Tian-pei, Wang Hai-ning, Liu Guo-qiang, Liu Zhe, Wang Yan-rong
Department of Endocrinology, Peking University Third Hospital, Beijing 100083, China.
Zhonghua Yi Xue Za Zhi. 2008 Nov 4;88(40):2817-20.
To investigate the IL-18 expression in the thyroid tissues of Hashimoto's thyroiditis (HT) and its cellular localization and the effect of interferon-gamma (IFN-gamma) on the interleukin- (IL)-18 expression in thyrocytes.
RT-PCR and immunohistochemistry were used to detect the IL-18 expression and its cellular localization in the thyroid tissues biopsy specimens of 6 HT patients with normal thyroid function, 6 normal thyroid specimens resected from patients with pharyngeal carcinoma, and 16 specimens of thyroid tissues adjacent to the thyroid adenoma obtained during operation. Thyrocytes were isolated, cultured, and exposed to IL-1beta, tumor necrosis factor-alpha (TNF-alpha), or IFN-gamma for 48 h. RT-PCR and Western blotting were used to detect the IL-18 expression.
IL-18 mRNA expression was at an extremely low levels in the normal thyroid tissues and at a significantly higher level in the thyroid tissues of HT. Immunohistochemical staining showed that IL-18 expression was augmented in the thyroid tissues of HT and was mainly localized in the thyroid follicular cells. The IL-18 mRNA expression in the isolated human thyrocytes was dose-dependently elevated by IFN-gamma rather than TNF-alpha or IL-1beta. Western blotting showed that pro-IL-18, but not mature IL-18, was detected in the lysates of the cultured human thyrocytes and the expression of pro-IL-18 was increased by IFN-gamma.
IL-18 expression is elevated in the thyroid follicular cells of HT. IL-18 is constitutively expressed in the isolated human thyrocytes and its expression is up-regulated by IFN-gamma. Therefore, interplay between IL-18 and IFN-gamma may have an important role in the thyrocytes destruction in HT.
研究桥本甲状腺炎（HT）甲状腺组织中白细胞介素18（IL-18）的表达及其细胞定位，以及γ干扰素（IFN-γ）对甲状腺细胞中IL-18表达的影响。
采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法，检测6例甲状腺功能正常的HT患者甲状腺组织活检标本、6例因咽癌切除的正常甲状腺标本以及16例手术中获取的甲状腺腺瘤旁甲状腺组织标本中IL-18的表达及其细胞定位。分离培养甲状腺细胞，分别用IL-1β、肿瘤坏死因子-α（TNF-α）或IFN-γ处理48小时，采用RT-PCR和蛋白质免疫印迹法检测IL-18的表达。
正常甲状腺组织中IL-18 mRNA表达极低，而HT甲状腺组织中表达显著升高。免疫组织化学染色显示，HT甲状腺组织中IL-18表达增强，主要定位于甲状腺滤泡细胞。IFN-γ可使分离的人甲状腺细胞中IL-18 mRNA表达呈剂量依赖性升高，而TNF-α或IL-1β无此作用。蛋白质免疫印迹法显示，培养的人甲状腺细胞裂解物中可检测到前体IL-18，而非成熟IL-18，且IFN-γ可增加前体IL-18的表达。
HT甲状腺滤泡细胞中IL-18表达升高。IL-18在分离的人甲状腺细胞中组成性表达，其表达受IFN-γ上调。因此，IL-18与IFN-γ之间的相互作用可能在HT甲状腺细胞破坏中起重要作用。
