曲古霉素A对CD14^+单核细胞活化及TLR4信号通路的影响  

Effects of trichostatin A on CD14^+ monocytes activation and TLR4 signal pathway

作　　者：王洋 堵培 高珂琴 杨爽[1] 贾素洁[1] WANG Yang, DU Pei, GAO Keqin, YANG Shuang, JIA Sujie(Department of Pharmacy, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan , China)

机构地区：[1]中南大学湘雅三医院药学部

出　　处：《中国临床药理学与治疗学》2018年第8期867-873,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：中南大学研究生自主探索创新基金(2017zzts865);国家自然科学基金(81370392)

摘　　要：目的:研究曲古霉素A(trichostatin A,TSA)对CD14^+单核细胞活化状态及Toll样受体4(TLR4)炎性信号通路的影响及其具体机制。方法:分离健康人外周血CD14^+单核细胞,用20nmol/L浓度TSA孵育24 h后收集细胞,RT-q PCR方法检测TLR4及下游炎症因子基因mRNA表达水平,以流式细胞分析检测细胞表面TLR4蛋白表达量,以Ch IP-q PCR方法检测TLR4基因启动子区组蛋白H3乙酰化水平变化,以Transwell法检测单核细胞趋化能力,以细胞黏附力实验检测单核细胞的黏附能力。结果:TSA刺激能够增加CD14^+单核细胞的趋化和黏附能力,上调CD14^+单核细胞中TLR4及下游炎症因子TNF-α、MCP-1和IL-6的表达,提高TLR4基因启动子区组蛋白H3乙酰化水平。结论:TSA能够诱导CD14^+单核细胞活化,提高TLR4启动子区组蛋白乙酰化修饰水平,促进TLR4信号通路基因过度表达。AIM： To study the effects of trichostatin A（TSA） on CD14^＋monocytes activation and TLR4 signal pathway. METHODS： CD14^＋monocytes were isolated from healthy donors and cultured in 1640 medium with 20 nmol/L TSA. After 24 hours,cells were harvested to detect the expression of TLR4 and downstream cytokines by RT-qPCR and flow cytometry methods. Ch IP-qPCR was used to detect histone H3 acetylation level TLR4 promoter. Transwell and adhesion experiments were performed to assess the motility and adhesion ability of CD14^＋monocytes. RESULTS： TSA treatment can increase the motility and adhesion ability of CD14^＋monocytes. Expression of TLR4 and down-stream cytokines,including TNF-α,MCP-1 and IL-6,were upregulated in CD14^＋monocytes after TSA treatment.Higher acetylation of histone H3 within TLR4 promoter region was also detected in CD14^＋monocytes after TSA treatment. CONCLUSION： TSA activates CD14^＋monocytes,promotes the expression of genes in TLR4 signal pathway and increases the histone H3 acetylation of TLR4 promoter.

关 键 词：曲古霉素A CD14^+单核细胞 组蛋白乙酰化 TLR4信号通路 细胞活化 

分 类 号：R363[医药卫生—病理学]