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

目的:本研究试图检测不同浓度17β雌二醇(F2)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MSC 24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.

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

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~(-8) and 10~(-7) mol/L).After cell counting,proliferation,adherent ability and immunophenotypes of MSC were detected by flowcytometry.The gene expressions of cytokine (IL-6,TGF-βand 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 (MHC Ⅱ,CD80 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.