组蛋白H4的乙酰化在急性冠脉综合征患者CD4^＋CD28^-T细胞CD28表达缺失中的作用  

The role of histone 4 acetylation in loss of CD28 on CD4^＋CD28^- T cells in patients with acute coronary syndrome

作　　者：桂琳[1] 任蕾[1] 刘军[1] 崔颖[1] 孙文英[1] 黄立娟[1] Gui Lin;Ren Lei;Liu Jun;Cui Ying;Sun Wenying;Huang Lijuan(Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China)

机构地区：[1]哈尔滨医科大学附属第二医院检验科,150081

出　　处：《国际免疫学杂志》2017年第6期604-607,共4页International Journal of Immunology

基　　金：国家自然科学基金面上项目（81371880）

摘　　要：目的通过对急性冠脉综合征（acute coronary syndrome，ACS）患者外周血CD4^＋T细胞CD28 mRNA水平和CD28基因启动子区域组蛋白H4（histone 4，H4）的乙酰化状态的研究，旨在探讨H4的乙酰化在ACS患者CD4^＋CD28^－T细胞CD28表达缺失中的作用。方法免疫磁珠法分离外周血CD4^＋T细胞，经逆转录实时定量PCR（Real time-PCR）技术检测CD4^＋T细胞CD28mRNA表达水平，染色质免疫共沉淀和实时荧光定量PCR技术（ChIP-qPCR）检测CD28启动子区域H4的乙酰化状态。结果与正常对照组相比，ACS患者CD4^＋T细胞CD28mRNA表达水平显著减低，差异具有统计学意义[正常对照组比ACS组：（1.063±0.131）比（0.739±0.065），t＝2.65，P〈0.05]。CD28基因启动子区域H4的乙酰化水平降低，差异具有统计学意义[正常对照组比ACS组：（3.115±0.545）比（1.275±0.168），t＝3.222，P〈0.05]。CD28基因启动子区域H4乙酰化化水平与CD28mRNA表达水平呈正相关（P＝0.03，r＝0.582）。结论ACS患者CD4＋T细胞CD28基因启动子区域H4低乙酰化调控了CD28基因转录抑制。Objective To investigate the role of histone 4 acetylation in CD28 expression in patients with acute coronary syndrome（ACS） by detecting the level of CD28 mRNA and the H4 acetylation status of CD28 promoter.Methods CD4^＋ T cells were isolated with magnetic activated cell sorting（MACS）. The mRNA levels of CD28 were determined by real time-PCR after reverse transcription.The H4 acetylation status of CD28 promoter regulatory sequences was detected by chromatin Immunoprecipitation and real time-PCR（ChIP-qPCR）.Results Compared with normal control, the mRNA levels of CD28 in CD4^＋ T cells were significantly lowered in patients with ACS （Control vs ACS： 1.063±0.131 vs 0.739±0.065, t=2.65, P〈0.05）. The H4 acetylation status of CD28 gene promoter region was lower than that of normal control （Control vs ACS： 3.115±0.545 vs 1.275±0.168）, t=3.222, P〈0.05）. A positive correlation was found between CD28 promoter H4 acetylation and CD28 mRNA level（P=0.03, r=0.582）.Conclusion CD28 gene promoter H4 deacetylation regulated the CD28 transcriptional repression in CD4^＋ T cells of ACS patients.

关 键 词：急性冠脉综合征 CD4^+CD28^-T细胞 组蛋白4 乙酰化 CD28基因启动子 

分 类 号：R446.6[医药卫生—诊断学] R541.4[医药卫生—临床医学]