组蛋白去乙酰化酶抑制剂罗米地辛对小鼠T细胞表型及功能的影响  

Influence of histone deacetylase inhibitor romidepsin on phenotype and function of T lymphocytes in vitro

作　　者：田孝军[1] 徐晶[2] 蒋继贫[3] 

机构地区：[1]荆州市第二人民医院重症医学科,湖北荆州434000 [2]华中科技大学同济医学院附属同济医院手术室,湖北武汉430030 [3]华中科技大学同济医学院附属同济医院器官移植研究所,湖北武汉430030

出　　处：《中国病理生理杂志》2015年第6期1099-1104,共6页Chinese Journal of Pathophysiology

摘　　要：目的:通过体外实验观察罗米地辛对效应T细胞和调节性T细胞的作用。方法:取CFSE标记的淋巴细胞、CD4+T细胞和CD8+T细胞作为反应细胞,实验组加入不同浓度梯度(1、3、5μmol/L)的罗米地辛及CD3/CD28单抗进行淋巴细胞培养,以仅加入CD3/CD28单抗作为阳性对照组,另设空白对照组。培养72 h后检测各组细胞的增殖情况。以淋巴细胞作为反应细胞,实验组、阳性对照组及空白对照组设定同上,72 h后检测各组中CD4+Foxp3+T细胞与CD4+T细胞的比例变化。同时采用ELISA检测培养液中相关细胞因子,如TNF-α、IL-10及TGF-β水平的变化。结果:罗米地辛剂量依赖性地抑制CD3/CD28单抗诱导的淋巴细胞、CD4+T细胞和CD8+T细胞的增殖(P<0.05)。在CD3/CD28单抗存在的条件下,1μmol/L的罗米地辛不能诱导CD4+Foxp3+T细胞的比例上调(P>0.05)。但提高罗米地辛的浓度至3μmol/L和5μmol/L后,CD4+Foxp3+T细胞的比例显著提高(P<0.05)。随着罗米地辛浓度的增加,TNF-α和IL-10水平呈剂量依赖性降低,但各实验组明显高于空白对照组而低于阳性对照组(P<0.05)。TGF-β在阳性对照组虽稍有升高,但与空白对照组相比无显著差异(P>0.05)。而随着罗米地辛浓度的增加,TGF-β水平呈剂量依赖性升高,3实验组间及与空白对照组、阳性对照组间差异显著(P<0.05)。结论:体外实验研究显示罗米地辛不仅能够有效抑制效应性T细胞的增殖,而且一定浓度的罗米地辛可上调调节性T细胞的比例,这可能与TGF-β升高有关,而与IL-10变化无关。AIM：To explore the effects of romidepsin （ FK228） , a novel histone deacetylase inhibitor, on the effector and regulatory T cells in vitro.METHODS：As the reactive cells, lymphocytes, CD4 ＋T cells and CD8 ＋T cells were labelled with CFSE, and stimulated with anti-CD3 and anti-CD28 mAbs in the presence and absence of different levels of romidepsin （experimental group and positive control group）, or PBS （placebo group）.After 72 h, the proliferation of the cells was detected in different groups.The lymphocytes were stimulated with anti-CD3 and anti-CD28 mAbs in the pres-ence and absence of different levels of romidepsin （ experimental group and positive control group ） , or PBS （ placebo group） .After 72 h, the percentage of CD4＋Foxp3 ＋T cells and the levels of related cytokines were detected in different groups.RESULTS：The proliferation of CFSE-labelled lymphocytes, CD4 ＋T cells and CD8＋T cells triggered by anti-CD3 and anti-CD28 mAbs all were inhibited when cultured with romidepsin at concentrations of 1 μmol/L, 3 μmol/L and 5 μmol/L in a dose-dependent manner （P〈0.05）.Compared with placebo group, in the presence of anti-CD3 and anti-CD28 mAbs, 1 μmol/L romidepsin did not increase the percentage of CD4 ＋Foxp3 ＋T cells （ P〉0.05 ） .When cultured with romidepsin at concentrations of 3 μmol/L and 5 μmol/L, the percentage of CD4 ＋ Foxp3 ＋T cells was enhanced markedly （ P〈0.05） .The levels of IL-10 and TNF-αin the supernatant were markedly increased in positive control group 〈br〉 and 3 experimental groups （ P〈0.05 ） , and the levels of cytokines in different experimental groups were gradually de-creased with the elevation of FK228 concentration （P〈0.05）.The level of TGF-βwas slightly increased in positive con-trol group with no significant difference compared with placebo group （P〉0.05）.With the increase in the concentration of FK228 in different experimental groups, the TGF-βlevel was increased in a dose-dependent manner and t

关 键 词：组蛋白去乙酰化酶 罗米地辛 调节性T细胞 

分 类 号：R392.1[医药卫生—免疫学]