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KMID : 0043320090320040613
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Archives of Pharmacal Research
2009 Volume.32 No. 4 p.613 ~ p.624
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Anti-inflammatory Effect of Trichostatin-A on Murine Bone Marrow-derived Macrophages
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Lee Jae-Kwon
Han Sang-Bae
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Abstract
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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-marrowderived 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 naive 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.
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KEYWORD
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Trichostatin-A, Anti-inflammation, Cytokine, Immunosuppressor, Histone deacetylase inhibitor, Hyperacetylation
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