Document Detail


HDAC inhibition and graft versus host disease.
MedLine Citation:
PMID:  21298214     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Histone deacetylase (HDAC) inhibitors are currently used clinically as anticancer drugs. Recent data have demonstrated that some of these drugs have potent antiinflammatory or immunomodulatory effects at noncytotoxic doses. The immunomodulatory effects have shown potential for therapeutic benefit after allogeneic bone marrow transplantation in several experimental models of graft versus host disease (GVHD). These effects, at least in part, result from the ability of HDAC inhibitors (HDACi) to suppress the function of host antigen presenting cells such as dendritic cells (DC). HDACi reduce the dendritic cell (DC) responses, in part, by enhancing the expression of indoleamine 2,3-dioxygenase (IDO) in a signal transducer and activator of transcription-3 (STAT-3) dependent manner. They also alter the function of other immune cells such as T regulatory cells and natural killer (NK) cells, which also play important roles in the biology of GVHD. Based on these observations, a clinical trial has been launched to evaluate the impact of HDAC inhibitors on clinical GVHD. The experimental, mechanistic studies along with the brief preliminary observations from the ongoing clinical trial are discussed in this review.
Authors:
Sung Choi; Pavan Reddy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2011-01-08
Journal Detail:
Title:  Molecular medicine (Cambridge, Mass.)     Volume:  17     ISSN:  1528-3658     ISO Abbreviation:  Mol. Med.     Publication Date:    2011 May-Jun
Date Detail:
Created Date:  2011-06-02     Completed Date:  2011-10-27     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  9501023     Medline TA:  Mol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  404-16     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Graft vs Host Disease / drug therapy,  metabolism*
Histone Deacetylase Inhibitors / therapeutic use*
Histone Deacetylases / metabolism
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
STAT3 Transcription Factor / metabolism
Grant Support
ID/Acronym/Agency:
AI075284/AI/NIAID NIH HHS; CA143379/CA/NCI NIH HHS; HL090775/HL/NHLBI NIH HHS; K23 AI091623/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Indoleamine-Pyrrole 2,3,-Dioxygenase; 0/STAT3 Transcription Factor; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

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