罗格列酮上调成人隐匿性自身免疫糖尿病患者CD4^＋T细胞Foxp3 mRNA的表达  

Rosiglitazone upregulates Foxp3 mRNA expression of CD4^＋ T cells in adults with latent autoimmune diabetes

作　　者：杨治芳[1] 周智广[1] 黄干[1] 彭健[1] 颜湘[1] 

机构地区：[1]中南大学湘雅二医院内分泌科,中南大学代谢内分泌研究所,中南大学糖尿病中心,长沙410011

出　　处：《中华微生物学和免疫学杂志》2008年第3期264-268,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家自然科学基金资助项目（30600298,30670991）;湖南省自然科学基金（06C0256）

摘　　要：目的观察罗格列酮对成人隐匿性自身免疫糖尿病（LADA）患者CD4^＋调节性T细胞的影响，旨在探讨罗格列酮的免疫调节机制。方法采用磁珠分离LADA患者CD4^＋T细胞，1、10和100μmol／L罗格列酮干预CD4^＋T细胞。MTT法检测细胞活性，^3H—TdR掺入法检测增殖抑制率。流式细胞术检测CD4^＋CD25^＋T细胞比值。RT-PCR检测过氧化物酶体增殖激活受体-γ（PPARγ）mRNA、TGF-β1mRNA表达，实时荧光定量PCR检测Foxp3 mRNA表达。结果CD4^＋T细胞表达PPARγ mRNA。罗格列酮抑制植物凝集素（PHA）刺激的CD4^＋T细胞增殖。1p．mol／L和10μmol／L组罗格列酮作用的CD4^＋CD25^＋T细胞比例无明显变化，100μmol／L组CD4^＋CD25^＋T细胞比例降低。10μmol／L罗格列酮上调CD4^＋T细胞的Foxp3mRNA表达，但TGF-β1mRNA表达无显著变化。小剂量IL-2参与下，10μmol／L罗格列酮（药理浓度范围内）升高CD4^＋T细胞Foxp3 mRNA表达。结论罗格列酮上调LADA患者CD4^＋T细胞Foxp3 mRNA表达，改善自身免疫耐受缺陷。Objective To investigate the effect of rosiglitazone on the CD4^＋ regulatory T cells in the patients with latent autoimmune diabetes in adults（LADA）. Methods The CD4^＋ T cells from LADA patients were isolated with anti-CD4-dynal magnetic beads. The expression of Foxp3 mRNA, along with peroxisome proliferators activator receptors gamma （PPARγ） mRNA and TGF-β1 mRNA was determined. The effect of rosiglitazone on CD4^＋ T cells was measured, after treated with rosiglitazone for 48 h. Cell viability was assessed by MTT assay. The proliferation was assayed with ^3H-TdR. Two-color staining （anti-CD4, anti-CD25 ） flow cytometric analysis was employed to measure the percentage of CD4^＋ CD25^＋ T cells of peripheral blood. Results PPARγmRNA was expressed in peripheral CD4^＋ T lymphocytos. Rosiglitazone inhibited phytohemagglutinin （PHA）-induced human CD4^＋ T cell proliferation in dose dependence. The percentage of CD4^＋ CD25^＋ T cells showed no significant change after the peripheral blood culture with 1 μmol/L and 10 μmol/L rosiglitazone. 10 μmol/L of rosiglitazone induced Foxp3 mRNA expression in vitro （3.27 fold,P 〈 0.05 ）, whereas TGF-β1 mRNA expression did not change. Furthermore, only 1 μmol/L of rosiglitazone could promote Foxp3 mRNA expression if adding IL-2 （10 U/ml） in cultures （3.48 fold, P 〈 0.05）. Conclusion Rosiglitazone promotes Foxp3 mRNA expression in CD4^＋ T cells in vivo and in vitro, improving the defective of the regulatory T cells.

关 键 词：糖尿病 自身免疫 隐匿性 CD4^+CD25^+T细胞 FOXP3 

分 类 号：R686[医药卫生—骨科学]