水仙环素抑制T细胞增殖的作用机制  

The mechanism of narciclasine inhibiting T cell proliferation

作　　者：张云惠 邓弘仙 吴利红 蒋海静 范诗逸 黄玲 罗兴燕 刘阳 赖翼[2,5] ZHANG Yunhui;DENG Hongxian;WU Lihong;JIANG Haijing;FAN Shiyi;HUANG Ling;LUO Xingyan;LIU Yang;LAI Yi(School of Pharmacy,Chengdu Medical College,Chengdu 610500,China;School of Laboratory Medicine,Chengdu Medical College,Chengdu 610500,China;Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-Origin Food,Chengdu Medical College,Chengdu 610500,China;School of Clinical Medicine,Chengdu Medical College,Chengdu 610500,China;Research Center,Chengdu Medical College,Chengdu 610500,Chin)

机构地区：[1]成都医学院药学院,610500 [2]成都医学院检验医学院,610500 [3]成都医学院临床医学院,610500 [4]成都医学院科研实验中心,610500 [5]四川省动物源性食品兽药残留防控技术工程实验室,成都610500

出　　处：《免疫学杂志》2021年第1期40-45,共6页Immunological Journal

基　　金：四川省教育厅重点项目(18ZA0143);植物化学与西部植物资源持续利用国家重点实验室开放项目(P2018-KF03);大学生创新创业训练计划项目(S201913705078)。

摘　　要：目的探究水仙环素抑制T细胞增殖与功能的作用机制。方法密度梯度离心法及免疫磁珠法纯化人外周血T细胞,anti-CD3/anti-CD28抗体活化T细胞。使用流式细胞仪检测细胞增殖、CD25的表达、细胞毒性及细胞周期;酶联免疫吸附试验检测细胞因子IL-2、IL-6、IL^(-1)7及IFN-γ的分泌水平。结果水仙环素抑制anti-CD3/anti-CD28抗体活化的T细胞增殖,IC_(50)为(0.011±0.001)μmol·L^(-1),且浓度达0.24μmol·L^(-1)也不影响静息T细胞的存活。水仙环素抑制活化T细胞表达CD25和分泌IL-2,阻滞T细胞周期于G_0/G_1期。水仙环素对细胞因子IL-6、IL^(-1)7及IFN-γ的抑制作用呈剂量依赖效应。结论水仙环素抑制T细胞增殖活化并显著抑制促炎细胞因子分泌,提示水仙环素有望成为先导化合物开发新型免疫抑制剂。This study was performed to investigate the mechanism of narciclasine in inhibiting human T cell proliferation.Human peripheral blood T cells were purified by density gradient centrifugation and immunomagnetic microbeads,then activated by anti-CD3/anti-CD28 mAbs.Flow cytometry was used to measure the cell proliferation,cell cycle,CD25 expression and cytotoxicity of resting T cells,while ELISA assay was used to detect the secretion of cytokines IL-2,IL-6,IL^(-1)7 and IFN-γ.Data showed that narciclasine inhibited the T cell proliferation activated by anti-CD3/anti-CD28 mAbs with an IC50 value of 0.011±0.001μmol·L^(-1),but had no effect on resting T cells survival,even at the concentration up to 0.24μmol·L^(-1).Narciclasine inhibited the expression of CD25 and IL-2 and induced T cell cycle arrest in G0/G1 phase.The inhibitory effects of narciclasine on IL-6,IL^(-1)7 and IFN-γwere dose-dependent.In conclusion,narciclasine inhibits the proliferation and activation of T cells,and also significantly inhibits the secretion of pro-inflammatory cytokines,suggesting that narciclasine may be a potential lead compound for the development of new types of immunosuppressant.

关 键 词：T细胞增殖 水仙环素 免疫抑制剂 流式细胞术 

分 类 号：R392.5[医药卫生—免疫学] R979.5[医药卫生—基础医学]