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 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.
Jung
I D
ID
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.
Lee
J S
JS
Jeong
Y I
YI
Lee
C M
CM
Chang
J H
JH
Jeong
S K
SK
Chun
S H
SH
Park
W S
WS
Han
J
J
Shin
Y K
YK
Park
Y-M
YM
D021581:Active Transport, Cell Nucleus; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D007378:Interleukins; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D016328:NF-kappa B; D010456:Peptides, Cyclic; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C102351:apicidin; C482199:lipopolysaccharide, E coli O55-B5; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases; D006655:Histone Deacetylases