Anti-inflammatory effect of Trichostatin-A on murine bone marrow-derived macrophages

Arch Pharm Res. 2009 Apr;32(4):613-24. doi: 10.1007/s12272-009-1418-4. Epub 2009 Apr 29.

Abstract

Histone deacetylase (HDAC) inhibitors were recently shown to suppress inflammatory responses in models of autoimmune and inflammatory diseases. In this study, the anti-inflammatory effects of five different HDAC inhibitors on lipopolysaccharide-(LPS)-stimulated macrophages were compared and the mechanisms of these effects were demonstrated. Trichostatin-A (TSA) and scriptaid, two of the five HDAC inhibitors, showed the most potent inhibitory effects on the nitric-oxide (NO) production of RAW264.7 cells and bone-marrow-derived macrophages (BMDMs). TSA significantly decreased the mRNA and protein levels of the proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta, whereas the pretreatment with TSA increased the level of the immunosuppressive cytokine IL-10. TSA also reduced the cell surface markers of the maturity of the macrophages. Furthermore, a longer duration (up to 8 h) of hyperacetylation was observed in the cells that had been exposed to TSA, whereas the hyperacetylation induced by the other HDAC inhibitors was absent after 8 h. These results demonstrated that TSA is the most potent HDAC inhibitor of histone deacetylation and has the greatest ability to induce anti-inflammatory activity in cloned and naïve macrophages. These results are expected to serve as a guide for future studies on the ability of HDAC inhibitors to inhibit acute and chronic inflammatory diseases.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Hydroxamic Acids / pharmacology*
  • Hydroxylamines / pharmacology
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / metabolism
  • Quinolines / pharmacology
  • RNA, Messenger / metabolism
  • Time Factors

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Hydroxylamines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Quinolines
  • RNA, Messenger
  • scriptaid
  • Nitric Oxide
  • trichostatin A
  • Histone Deacetylases