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中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (8): 867-873.doi: 10.12092/j.issn.1009-2501.2018.08.005

• 基础研究 • 上一篇    下一篇

曲古霉素A对CD14+单核细胞活化及TLR4信号通路的影响

王 洋,堵 培,高珂琴,杨 爽,贾素洁   

  1. 中南大学湘雅三医院药学部,长沙 410013,湖南
  • 收稿日期:2018-04-19 修回日期:2018-05-08 出版日期:2018-08-26 发布日期:2018-08-28
  • 通讯作者: 贾素洁,女,博士,硕士生导师,研究方向:表观遗传学。 Tel:0731-88618458 E-mail:sujiejia@csu.edu.cn
  • 作者简介:王洋,男,硕士研究生,研究方向:表观遗传学因素与心血管疾病。
  • 基金资助:

    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)

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

WANG Yang, DU Pei, GAO Keqin, YANG Shuang, JIA Sujie   

  1. Department of Pharmacy, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China
  • Received:2018-04-19 Revised:2018-05-08 Online:2018-08-26 Published:2018-08-28

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20 nmol/L浓度TSA孵育24 h后收集细胞,RT-qPCR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ChIP-qPCR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。

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

Abstract:

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. ChIP-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 up-regulated 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.

Key words: trichostatin A, CD14+ monocytes, histone acetylation, TLR4 signal pathway, cell activation

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