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Trichostatin A inhibits inflammation in phorbol myristate acetate‑induced macrophages by regulating the acetylation of histone and/or non‑histone proteins.

Abstract
Histone deacetylase inhibitors (HDACi) are currently used in the routine clinical treatment of cancer. Alongside the antitumor activity of HDACi, increased attention has been paid to their anti‑inflammatory effects. The present study aimed to analyze the inhibitory effects of the HDACi Trichostatin A (TSA), on the release of inflammatory mediators from macrophages differentiated from U‑937 cells. A low dose of TSA (50 nM) was able to effectively decrease the levels of inflammatory cytokines in the cell supernatants, independent of apoptosis. In addition, the potential underlying mechanisms were explored, and TSA was shown to promote, rather than inhibit, the acetylation of histones. Furthermore, the inflammation‑induced enhanced expression of class I HDACs was effectively inhibited by TSA. In addition, TSA enhanced the lipopolysaccharide (LPS)‑induced expression of cyclooxygenase‑2, but suppressed the LPS‑induced expression of chemokine (C‑C motif) ligand 7. The acetylation level of nuclear factor‑κB p65 was decreased by LPS, but increased following treatment with TSA. In conclusion, TSA was able to inhibit inflammation in macrophages. However, whether the mechanism by which TSA inhibits inflammation is through significantly enhancing histone acetylation, in order to selectively suppress the expression of proinflammatory genes, and/or through regulating non‑histone acetylation requires further research.
AuthorsQian Zhang, Fan Yang, Xun Li, Luwen Wang, Xiaogang Chu, Hong Zhang, Zuojiong Gong
JournalMolecular medicine reports (Mol Med Rep) Vol. 13 Issue 1 Pg. 845-52 (Jan 2016) ISSN: 1791-3004 [Electronic] Greece
PMID26647731 (Publication Type: Journal Article)
Chemical References
  • Cytokines
  • Histones
  • Hydroxamic Acids
  • Transcription Factor RelA
  • trichostatin A
  • Histone Deacetylases
  • Tetradecanoylphorbol Acetate
Topics
  • Acetylation (drug effects)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Cytokines (metabolism)
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation (drug effects)
  • Histone Deacetylases (metabolism)
  • Histones (metabolism)
  • Humans
  • Hydroxamic Acids (pharmacology)
  • Inflammation (genetics, pathology)
  • Macrophages (metabolism, pathology)
  • Tetradecanoylphorbol Acetate
  • Transcription Factor RelA (metabolism)

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