Document Detail


Apicidin, the histone deacetylase inhibitor, suppresses Th1 polarization of murine bone marrow-derived dendritic cells.
MedLine Citation:
PMID:  19505402     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Apicidin is a fungal metabolite shown to exhibit anti-proliferative, anti-invasive, and anti-inflammatory properties by the inhibition of histone deacetylase (HDAC). However, the effects of apicidin on the maturation and immunostimulatory function of dendritic cells (DCs) remain unknown. In this study, we investigated whether apicidin modulates surface molecule expression, cytokine production, endocytosis capacity, and underlying signaling pathways in murine bone marrow-derived DCs. We observed that apicidin significantly attenuated surface molecule expression in LPS-stimulated DCs, suppressed production of interleukin (IL)-12 and proinflammatory cytokines (IL-6 and TNF-alpha) by DCs, and reduced IFN-gama production by T cells. The apicidin-treated DCs were found to be highly efficient in antigen capture via mannose receptor-mediated endocytosis. Apicidin also inhibited LPS-induced MAPK activation and NF-kB nuclear translocation in DCs. Moreover, the apicidin-treated DCs were incapable of inducing Th1 responses and normal cell-mediated immune responses. These novel findings not only provide new insights into the immunopharmacological role of apicidin in terms of its effects on DCs, but also broaden current perspectives of the immunopharmacological functions of apicidin, and have implications for the development of therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.
Authors:
I D Jung; J S Lee; Y I Jeong; C M Lee; J H Chang; S K Jeong; S H Chun; W S Park; J Han; Y K Shin; Y-M Park
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of immunopathology and pharmacology     Volume:  22     ISSN:  0394-6320     ISO Abbreviation:  Int J Immunopathol Pharmacol     Publication Date:    2009 Apr-Jun
Date Detail:
Created Date:  2009-06-09     Completed Date:  2009-07-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8911335     Medline TA:  Int J Immunopathol Pharmacol     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  501-15     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology and National Research Laboratory of Dendritic Cell Differentiation & Regulation, Medical Research Institute, College of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-Do, Busan.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Adjuvants, Immunologic / pharmacology*
Animals
Bone Marrow Cells / drug effects*,  enzymology,  immunology
Cells, Cultured
Dendritic Cells / drug effects*,  enzymology,  immunology
Dose-Response Relationship, Drug
Endocytosis / drug effects
Enzyme Inhibitors / pharmacology*
Histone Deacetylase Inhibitors*
Histone Deacetylases / metabolism
Interferon-gamma / metabolism
Interleukins / metabolism
Lectins, C-Type / metabolism
Lipopolysaccharides / pharmacology
Male
Mannose-Binding Lectins / metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases / metabolism
NF-kappa B / metabolism
Peptides, Cyclic / pharmacology*
Phosphorylation
Receptors, Cell Surface / metabolism
Th1 Cells / immunology*
Tumor Necrosis Factor-alpha / metabolism
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Interleukins; 0/Lectins, C-Type; 0/Lipopolysaccharides; 0/Mannose-Binding Lectins; 0/NF-kappa B; 0/Peptides, Cyclic; 0/Receptors, Cell Surface; 0/Tumor Necrosis Factor-alpha; 0/apicidin; 0/lipopolysaccharide, E coli O55-B5; 0/mannose receptor; 82115-62-6/Interferon-gamma; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.5.1.98/Histone Deacetylases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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