桥本病中白细胞介素18表达可能参与甲状腺细胞的自我毁损过程

目的 观察白细胞介素18(IL-18)在桥本病甲状腺组织中的表达及其细胞定位,并探讨干扰素γ(IFN-γ)对甲状腺细胞中IL-18表达的影响.方法 采用逆转录-聚合酶链反应(RT-PCR)和免疫组织化学染色,检测IL-18在正常和桥本病甲状腺组织中的表达及其细胞定位.原代培养的人甲状腺细胞与IL-1B、肿瘤坏死因子α(TNF-α)或IFN-γ孵育后,应用RT-PCR和Western印迹检测IL-18表达的变化.结果 新鲜甲状腺组织的RT-PCR分析显示,IL-18 mRNA在正常甲状腺组织中表达水平极低,但在桥本病的甲状腺组织中表达显著增高,IL-18/β-肌动蛋白的灰度比分别为0.15±0.02和0.90±0.13(P<0.05).免疫组织化学染色显示,IL-18表达在桥本病的甲状腺组织中明显增加,且主要定位于甲状腺滤泡上皮细胞.在离体培养的甲状腺上皮细胞中,IFN-γ可剂量依赖性增加IL-18 mRNA的表达,而TNF-α和IL-1β则无类似的效应.Western印迹显示,IL-18原在离体甲状腺细胞中可见表达,IFN-γ使IL-18原表达增加.结论 IL-18在桥本病的甲状腺滤泡上皮细胞中表达明显增加,IFN-γ可上调离体甲状腺细胞IL-18表达.IL-18与IFN-γ之间的相互作用在桥本病的甲状腺细胞破坏中可能具有重要的意义.

Thyrocytes contribute to their own demise: the role of interleukin-18 in Hashimoto's thyroiditis

Objective To investigate the IL-18 expression in the thyroid tissues of Hashimoto's thyroiditis (HT) and its cellular localization and the effect of interferon-γ(IFN-γ) on the interleukin- (IL)-18 expression in thyrocytes. Methods RT-PCR and immunohistoehemistry 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-1β, tumor necrosis factor-α (TNF-α), or IFN-γ for 48 h. RT-PCR and Western blotting were used to detect the IL-18 expression. Results 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. Immunohistoehemical 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-γ rather than TNF-α or IL-1β. 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-γ. Conclusion 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-γ. Therefore, interplay between IL-18 and IFN-γ may have an important role in the thyrocyte destruction in HT.