Apicidin, the histone deacetylase inhibitor, suppresses Th1 polarization of murine bone marrow-derived dendritic cells.
Int J Immunopathol Pharmacol
; 22(2): 501-15, 2009.
Article
em En
| MEDLINE
| ID: mdl-19505402
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos Cíclicos
/
Células Dendríticas
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Células da Medula Óssea
/
Adjuvantes Imunológicos
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Células Th1
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Inibidores Enzimáticos
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Inibidores de Histona Desacetilases
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article