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

Article

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)-α, interleukin (IL)-6, and IL-1β, 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.

Key words

Trichostatin-A Anti-inflammation Cytokine Immunosuppressor Histone deacetylase inhibitor Hyperacetylation 

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© The Pharmaceutical Society of Korea 2009

Authors and Affiliations

  1. 1.College of PharmacyChungbuk National UniversityCheongjuKorea
  2. 2.Department of Biology Education, College of EducationChungbuk National UniversityCheongjuKorea

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