Open AccessApicidin, the Histone Deacetylase Inhibitor, Suppresses TH1 Polarization of Murine Bone Marrow-Derived Dendritic Cells
Author(s) -
Jung Id,
Jae Sung Lee,
Jeong Yi,
Lee Cm,
Chang Jh,
Jeong Sk,
Chun Sh,
WS Park,
Jin Han,
Young Kee Shin,
Y-M Park
Publication year - 2009
Publication title -
international journal of immunopathology and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.724
H-Index - 53
eISSN - 2058-7384
pISSN - 0394-6320
DOI - 10.1177/039463200902200227
Subject(s) - proinflammatory cytokine , chemistry , microbiology and biotechnology , cancer research , histone deacetylase , dendritic cell , bone marrow , cytokine , immune system , mapk/erk pathway , immunology , signal transduction , inflammation , medicine , biology , histone , biochemistry , gene
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.