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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2018, Vol. 23 ›› Issue (8): 867-873.doi: 10.12092/j.issn.1009-2501.2018.08.005

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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

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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