17β-雌二醇抑制星形胶质细胞趋化Th17细胞的机制  

17β-E2 Inhibits Th17 Cells Migration by IFN-γ Activated Astrocytes

作　　者：邱伟[1] 徐文[1] 李蕊[1] 戴永强[1] 王玉鸽[1] 孙晓渤[1] 陆正齐[1] 胡学强[1] 

机构地区：[1]中山大学附属第三医院神经病学科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2014年第5期702-709,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：中山大学高校基本业务费青年教师培育项目(12ykpy36);中山大学附属第三医院杰出青年后备人才培养计划基金

摘　　要：【目的】本研究旨在明确17β-E2能否通过阻断星形胶质细胞表达抗原提呈相关分子(MHCⅡ、CD80和CD86)和抑制细胞因子分泌,从而抑制其对Th17细胞的趋化作用。【方法】原代培养的小鼠星型胶质细胞分为5组:未处理组、IFN-γ(20 ng/mL)处理组、IFN-γ(20 ng/mL)+17β-E2(0.28 ng/mL)处理组、IFN-γ(20 ng/mL)+17β-E2(2.75 ng/mL)处理组和IFN-γ(20 ng/mL)+17β-E2(27.50 ng/mL)处理组。Western blotting检测未处理组和IFN-γ(20 ng/mL)处理组星形胶质细胞ERα和ERβ表达。免疫荧光检测各处理组星形胶质细胞MHCⅡ表达。流式细胞术检测各处理组星形胶质细胞MHCⅡ及协同刺激分子表达。ELISA检测各组星形胶质细胞分泌IL-17和TGF-β情况。趋化实验检测各处理组星形胶质细胞条件培养基体外趋化Th17细胞的能力。【结果】IFN-γ诱导星形胶质细胞ERα表达上调,对ERβ表达无明显影响。不同浓度17β-E2处理均明显降低星形胶质细胞MHCⅡ及协同刺激分子的表达。27.50 ng/mL浓度的17β-E2可抑制IFN-γ活化星形胶质细胞产生IL-17,而对TGF-β无明显影响。2.75 ng/mL浓度的17β-E2可抑制IFN-γ活化星形胶质细胞趋化Th17细胞。【结论】本研究的结果表明17β-E2可能部分通过抑制炎症活化的星形胶质细胞表达MHCⅡ、CD80、CD86及分泌炎性因子抑制对Th17细胞的趋化作用。[Ojective] The current study was designed to determine whether 17β-E2 decrease Th17 cell migration by inhibiting MHC Ⅱ expression and cytokines secretion （focus on IL-17 and TGF-β） in astrocytes.[Methods] Primary astrocyte cultures were treated as follows：untreated,treat with IFN-γ （20 ng/mL） alone or in combination with 0.28 ng/mL,2.75 ng/mL,27.50 ng/mL 17β-E2 for 36 h.ERα and ERβ expression in astrocytes with different treatment were detected by western blotting.MHC Ⅱ expression were analyzed by immunofluorescence and flow cytometry.Co-stimulatroy molecules expression were analysed by flow cytometry.IL-17 and TGF-β secretion were examined by ELISA.Th17 cells migration was detected by transwell assay.[Results] IFN-γinduce the expression of ERα,but not ERβ.17β-E2 treatment at different concentrations from 0.28 ng/mL to 27.50 ng/mL significantly decreased MHC Ⅱ and co-stimulatory molecules expression in IFN-γ activated astrocytes.17β-E2 at 27.50 ng/mL significantly inhibited IL-17 production in IFN-γactivated astrocytes,but had no effect on TGF-β secretion.17β-E2 at 2.75ng/mL decreased Th17 cells migration by IFN-γactivated astrocytes.[Conclusions] These data demonstrate that 17β-E2 decreases Th17 cells migration partially via inhibiting MHC Ⅱ expression and IL-17 secretion in IFN-γactivated astrocytes.

关 键 词：17Β-雌二醇 星形胶质细胞 MHCⅡ IL-17 

分 类 号：R392.5[医药卫生—免疫学]