雌激素通过调节MSC分泌细胞因子影响其对DC成熟与功能的抑制  

Estrogen can alter the immuno-suppressive effects of MSC on DC via modulating MSC's cytokine secretion

作　　者：赵叶琳[1] 赵晓寅[1] 孙凌云[2] 侯亚义[1] 

机构地区：[1]南京大学医学院免疫与生殖生物学实验室,南京210093 [2]南京大学医学院附属鼓楼医院风湿免疫科,南京210008

出　　处：《中国免疫学杂志》2010年第1期41-45,50,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(No.30771959);江苏省自然科学基金(No.2006119)资助

摘　　要：目的:本研究试图检测不同浓度17β-雌二醇(E2)存在的情况下人胎肺间充质干细胞(MSC)增殖和表型的变化,并分析这种状态的MSC对树突状细胞(DC)成熟和功能影响及其可能的机制。方法:分离培养人胎肺MSC,加入不同浓度E2,在24小时后对MSC进行细胞计数、测定其增殖和贴壁能力,并用流式细胞仪分析MSC表面标志,RT-PCR测定MSC中细胞因子(IL-6、TGF-β和VEGF)mRNA的表达情况。进一步探讨了E2处理24小时后的MSC对DC成熟和功能的影响。结果:分离得到的MSC纯度达到95%以上;E2影响MSC的增殖和贴壁能力,但不影响MSC表面标记的表达;MSC与DC共培养后DC表面CD86、MHCⅡ和CD80的表达均有所降低,而当DC与经E2预处理过的MSC共培后,DC表面MHCⅡ、CD80和CD86的表达回升;高浓度E2作用MSC24小时后,MSC表达的TGF-β与对照组相比减少,而IL-6和VEGF与对照组相比增加。结论:E2可能通过调节MSC分泌细胞因子的水平,改变MSC对DC的免疫抑制作用。Objective：To investigate the effects of 17β-Estradiol （E2） on mesenchymal stem cells （MSC） and to evaluate the＇effects of MSC treated with E2 on the maturation and function of dendritic cells （DC）. Methods： We first isolated and cultured MSC from the human fetal lung. The MSC were treated with E2 for 24 hours at various concentrations （10-9,10-s and 10-7 tool/L）. After cell counting, proliferation, adherent ability and immunophenotypes of MSC were detected by flowcytometry. The gene expressions of cytokine （IL-6, TGF-β and VEGF） were measured by RT-PCR.The effects of MSC treated with E2 on the maturation and function of DC were determined. Results： After treated with E2, the proliferation and adherent ability of MSC were increased, while the immunophenotypes of MSC were not affected. When MSCs co-cultured with DC, MSC could inhibit the immuophenotypes and function of DC. However, when DC co-cultured with E2-pretreated MSC, the immunophenotypes （MHCⅡ, CDSO and CD86） of DC had been reconstructed. After treated with the high concentration of E2 for 24 hours, MSC secreted lower level of TGF-β than that in the control group, while IL-6 and VEGF expressions were increased compared with those in the control group. Conclusion： Estrogen may alter the immuno-suppressive effects of MSC on DC via modulating the cytokine secretion of MSC.

关 键 词：雌激素 间充质干细胞 树突状细胞 系统性红斑狼疮 

分 类 号：R392[医药卫生—免疫学]