Histone deacetylase inhibitors decrease the antigen presenting activity of murine bone marrow derived dendritic cells

Once activated by infected pathogens, dendritic cells (DCs) undergo activation and release inflammatory mediators responsible for the signs of inflammation. Our aim was to elucidate whether histone deacetylase inhibitors (HDACIs), trichostatine-A (TSA), scriptaid (ST) and sodium butylate (SB) regulate the inflammatory response of DCs. Pre-treatment with TSA and ST reduced the syngeneic and allogeneic-antigen presenting activity of LPS-stimulated DCs in a dose dependent manner to statistical significance. SB also reduced the antigen presenting activity of DCs, but not significantly. HDACIs mediate their effects through the modulation of DC maturation and pre-treatment of the DCs with TSA or ST prior to treatment with LPS reduced the expressions of DC mature markers to the level of immature dendritic cells (iDCs). Moreover, TSA and ST reduced the IL-2 production from LPS-stimulated mature DCs. Our results suggest that HDACIs may actively modulate the DC-induced inflammatory response through inhibition of phenotypical or functional maturation. (C) 2009 Elsevier Inc. All rights reserved.