IFN-γ上调桥本甲状腺炎Fas表达介导甲状腺破坏

摘要

Objective To investigate the influence and mechanism of IFN-γ on the expression of Fas in Hashimoto thyrioditis.Methods ① The expressions of IFN-γ,Fas in Hashimoto thyrioditis and normal control were investigated by immunohistochemical staining;② The FRTL-5 cells were cultured in vitro,treated with IFN-γ at different concentration in different time.Quantitative RT-PCR and flow cytometry assay were used to examine the expressions of Fas mRNA and protein respectively.Results ① The staining of Fas in thyroid follicles and IFN-γ in lymphocytes in HT samples were strongly observed compared to normal controls.In addition,Fas protein positive thyroid follicular cells were common in lymphocyte infiltration areas;② The expression of Fas mRNA in FRTL-5 cells induced by IFN-γ had time-concentration dependent relation within certain ranges(P<0.05);③ The expression level of Fas on FRTL-5 cells treated with IFN-γ was significantly higher than that of normal control by flow cytometry assay.Conclusion IFN-γ mediated thyroid follicular cells apoptosis by up-regulating the expressions of Fas in HT.%目的 探讨干扰素-γ(IFN-γ)对桥本甲状腺炎(HT)Fas表达的影响及可能致病因素.方法 ① 采用免疫组织化学方法检测HT和正常甲状腺组织中IFN-γ及Fas的表达和分布;② 不同浓度、不同时间IFN-γ刺激大鼠甲状腺细胞系(FRTL-5细胞),采用实时荧光定量PCR、流式细胞术方法分别检测FRTL-5细胞Fas mRNA和蛋白的表达.结果 ① HT组织中甲状腺滤泡细胞Fas蛋白、淋巴细胞IFN-γ蛋白的表达显著高于正常甲状腺组织,且Fas阳性甲状腺滤泡细胞常见于淋巴细胞浸润区;② IFN-γ与FRTL-5细胞Fas mRNA表达水平存在时间-剂量依赖关系,差异有统计学意义(P<0.05);③ 流式细胞术测定经IFN-γ作用的FRTL-5细胞表面Fas表达水平显著高于未经IFN-γ刺激的FRTL-5细胞.结论 IFN-γ通过上调Fas的表达介导甲状腺滤泡细胞凋亡.