Apicidin, the Histone Deacetylase Inhibitor, Suppresses TH1 Polarization of Murine Bone Marrow-Derived Dendritic Cells

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 stu...

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Bibliographic Details
Published in:International journal of immunopathology and pharmacology 2009-04, Vol.22 (2), p.501-515
Main Authors: Jung, I.D., Lee, J.S., Jeong, Y-I., Lee, C-M., Chang, J.H., Jeong, S.K., Chun, S.H., Park, W.S., Han, J., Shin, Y.K., Park, Y-M.
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Adjuvants, Immunologic - pharmacology
Animals
Bone Marrow Cells - drug effects
Bone Marrow Cells - enzymology
Bone Marrow Cells - immunology
Cells, Cultured
Dendritic Cells - drug effects
Dendritic Cells - enzymology
Dendritic Cells - 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
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Summary: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-α) by DCs, and reduced IFN-γ 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-κB 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.
ISSN:0394-6320
2058-7384
DOI:10.1177/039463200902200227