CD4^+CD25^+调节T细胞对内皮细胞炎性因子分泌的影响  

CD4^+CD25^+ regulatory T cells modulate oxidized low density lipoprotein mediated VCAM-1,MCP-1 and IL-6 expression in human umbilical vein endothelial cells

作　　者：何少林[1] 李大主[1] 黎明[1] 马旭明[1] 林静[1] 昌薇[1] 赵卉[1] 

机构地区：[1]华中科技大学同济医学院协和医院心内科,武汉430022

出　　处：《中国免疫学杂志》2010年第12期1064-1068,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金资助项目(No.30670855)

摘　　要：目的:探讨CD4+CD25+调节性T细胞(Tregs)对氧化型低密度脂蛋白(ox-LDL)诱导人脐静脉内皮细胞(HU-VECs)VCAM-1、MCP-1、IL-6表达的影响。方法:磁性细胞分离器(MACS)分离CD4+CD25+T细胞及CD4+CD25-T细胞。在ox-LDL作用下,将内皮细胞分别与anti-CD3mAb激活的CD4+CD25+T细胞,CD4+CD25-T细胞共培养24小时。分别应用流式细胞术、ELISA、real-timePCR测定Tregs对ox-LDL诱导损伤HUVECs炎性因子VCAM-1、MCP-1、IL-6表达的影响。应用Transwell小室及中和抗体实验观察Tregs作用于HUVECs的具体机制。结果:与对照组比较,Tregs细胞可显著抑制ox-LDL诱导损伤HU-VECs炎性因子VCAM-1、MCP-1、IL-6的表达;被Transwell隔离或加入中和性抗体anti-IL-10/anti-TGF-β后,Tregs对HUVECs的抑制作用可被部分逆转。结论:Tregs细胞可显著抑制ox-LDL诱导损伤HUVECs炎性因子的表达,其作用机制既依赖于细胞直接接触,又依赖于细胞因子。Objective：To investigate the effects of CD4＋CD25＋ regulatory T cells（Tregs）on oxidized low-density lipoprotein（ox-LDL）-mediated VCAM-1,MCP-1 and IL-6 expression in human umbilical vein endothelial cells（HUVECs）.Methods：HUVECs were incubated alone（noT）,with Tregs（25＋）,or CD4＋CD25-T cells（25-）in the presence of anti-CD3 mAbs for 48 h,then were stimulated with ox-LDL for an additional 24 h.Flow cytometry and ELISA were used to measure the expression of inflammatory cytokines like vascular cell adhesion molecule-1（VCAM-1）,monocyte chemoattractant protein-1（MCP-1）and interleukin-6（IL-6）in HUVECs responding to ox-LDL,respectively.Transwell experiments were carried to investigate whether suppression of HUVECs inflammatory cytokine expression depended on cell contact or soluble factors.Results：The protein levels of inflammatory cytokines expression in HUVECs were determined by Flow cytometry or ELISA,which showed a significant reduction of inflammatory cytokines（VCAM-1：13.5%±4.0%;MCP-1：16.6±2.0 ng/ml;IL-6：1.9±0.8 ng/ml）in 25＋ system compared with that in noT system（VCAM-1：57.6%±5.2%;MCP-1：42.4±5.8 ng/ml;IL-6：8.8±1.4 ng/ml）or 25-system（VCAM-1：58.1%±7.1%;MCP-1：46.7±4.0 ng/ml;IL-6：9.3±1.7 ng/ml）.The similar effects of Tregs on the mRNA levels of inflammatory cytokine expression in HUVECs were obtained.Moreover,mechanistic studies revealed that Tregs-mediated suppression of the HUVECs response to ox-LDL required both cell contact and soluble factors.Conclusion：Tregs are able to inhibit the inflammatory cytokines like VCAM-1,MCP-1 or IL-6 response of HUVECs to ox-LDL,which depends on cell contact as well as soluble factors.

关 键 词：CD4+CD25+调节性T细胞 人脐静脉内皮细胞 氧化型低密度脂蛋白 炎性因子 TRANSWELL 

分 类 号：R392.12[医药卫生—免疫学]