IFN-γ上调桥本甲状腺炎Fas表达介导甲状腺破坏

IFN-γ mediates thyroid injury by upregulating Fas expression in Hashimoto thyroiditis

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 m RNA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 m RNA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。

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 investiga- ted 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 lympho- cytes 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 in- duced 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 cytome- try assay. Conclusion IFN-γ mediated thyroid follicular cells apoptosis by up-regulating the expressions of Fas in HT.