Open Access

SirT1 activator represses the transcription of TNF‑α in THP‑1 cells of a sepsis model via deacetylation of H4K16

  • Authors:
    • Guo‑Dong Chen
    • Wei‑Dong Yu
    • Xiao‑Ping Chen
  • View Affiliations

  • Published online on: November 15, 2016     https://doi.org/10.3892/mmr.2016.5942
  • Pages: 5544-5550
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sepsis is a systemic inflammatory response resulting from the excessive production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)‑α. Sirtuin 1 (SirT1) actively deacetylates histone proteins, and facilitates chromatin compaction and gene silencing. In the present study, a cell model of sepsis, comprising lipopolysaccharide (LPS)‑tolerant THP‑1 cells, was used to investigate whether the SirT1 activator, resveratrol, repressed the transcription of TNF‑α. Chromatin immunoprecipitation and real‑time PCR were used to determine the transcription of the TNF‑α promoter. The result revealed that the binding of SirT1 to the TNF‑α promoter was decreased by LPS stimulation in normal cells. However, in LPS‑tolerant cells, nuclear protein levels of SirT1 remained elevated, and LPS stimulation had no significant effect on the binding of SirT1 to the TNF‑α promoter. However, the activity of SirT1 was increased and binding of ace‑H4K16 to the TNF‑α promoter was decreased with resveratrol treatment in the tolerant cells. It was concluded that resveratrol stimulated sirtuin activity in LPS‑tolerant THP‑1 cells, and repressed TNF‑α transcription through the deacetylation of H4K16, without affecting the methylation of H3K9. Resveratrol offers potential as an infective candidate to alleviate inflammation in patients with sepsis.
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December-2016
Volume 14 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Chen GD, Yu WD and Chen XP: SirT1 activator represses the transcription of TNF‑α in THP‑1 cells of a sepsis model via deacetylation of H4K16. Mol Med Rep 14: 5544-5550, 2016.
APA
Chen, G., Yu, W., & Chen, X. (2016). SirT1 activator represses the transcription of TNF‑α in THP‑1 cells of a sepsis model via deacetylation of H4K16. Molecular Medicine Reports, 14, 5544-5550. https://doi.org/10.3892/mmr.2016.5942
MLA
Chen, G., Yu, W., Chen, X."SirT1 activator represses the transcription of TNF‑α in THP‑1 cells of a sepsis model via deacetylation of H4K16". Molecular Medicine Reports 14.6 (2016): 5544-5550.
Chicago
Chen, G., Yu, W., Chen, X."SirT1 activator represses the transcription of TNF‑α in THP‑1 cells of a sepsis model via deacetylation of H4K16". Molecular Medicine Reports 14, no. 6 (2016): 5544-5550. https://doi.org/10.3892/mmr.2016.5942