| Impact of valproic acid on dendritic cells function. | |
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MedLine Citation:
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PMID: 22209114 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Recent data suggested that histone deacetylase (HDAC) inhibitors possessed potent anti-inflammatory and immunomodulatory properties both in vitro and in vivo. This study assayed the ability of the HDAC inhibitor, valproic acid (VPA), to influence the differentiation and functional properties of dendritic cells (DCs) generated from circulating peripheral blood monocytes. METHODS AND RESULTS: Culture of monocytes in the presence of 0.5mM of VPA did not impair DC differentiation. However, on the phenotypic level, in mature DCs, CD40, CD80 and CD86 were downregulated in the presence of VPA, compared to mature DCs generated in the absence of VPA. VPA led also to a significant down-regulation of CD83 and HLA-DR expression on mature DCs. Moreover, VPA treatment significantly inhibited IL-10 and IL-12p70 production by mature DCs. IL-10 and IL-12p70 altered secretion was observed whether DCs were matured with LPS alone or with LPS and IFN-gamma. In an allogeneic mixed lymphocyte reaction, the proportion of IFN-gamma+CD4+ T cells was decreased (26% vs. 51%, p=0.005) when T cells were stimulated with DCs exposed to VPA. Also, CD8+ T cells stimulated with DCs treated with VPA, exhibited a significant decrease of Granzyme B expression. CONCLUSION: These results suggest that HDAC inhibition by VPA alters essential human DC functions, highlighting the need for monitoring of immune functions in cancer patients receiving HDAC inhibitors, but also making these drugs attractive therapies in inflammatory, and autoimmune diseases. |
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Authors:
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Jihane Frikeche; Thomas Simon; Eolia Brissot; Marc Grégoire; Béatrice Gaugler; Mohamad Mohty |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-8 |
Journal Detail:
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Title: Immunobiology Volume: - ISSN: 1878-3279 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2012-1-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8002742 Medline TA: Immunobiology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier GmbH. |
Affiliation:
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INSERM CRNCA UMR892, Nantes, France; Université de Nantes, Nantes, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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