histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in skg mice组蛋白脱乙酰酶抑制改变树突细胞承担耐受性表型和改善关节炎小鼠热议.pdfVIP

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histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in skg mice组蛋白脱乙酰酶抑制改变树突细胞承担耐受性表型和改善关节炎小鼠热议.pdf

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histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in skg mice组蛋白脱乙酰酶抑制改变树突细胞承担耐受性表型和改善关节炎小鼠热议

Misaki et al. Arthritis Research Therapy 2011, 13:R77 /content/13/3/R77 RESEARCH ARTICLE Open Access Histone deacetylase inhibition alters dendritic cells to assume a tolerogenic phenotype and ameliorates arthritis in SKG mice 1,2 1* 2 1 1 1 Kenta Misaki , Akio Morinobu , Jun Saegusa , Shimpei Kasagi , Masaaki Fujita , Yoshiaki Miyamoto , Fumichika Matsuki2 and Shunichi Kumagai1,2 Abstract Introduction: The purpose of this study was to elucidate the effects of histone deacetylase inhibition on the phenotype and function of dendritic cells and on arthritis in SKG mice. Methods: Arthritis was induced in SKG mice by zymosan A injection. Trichostatin A, a histone deacetylase inhibitor, was administered and its effects on arthritis were evaluated by joint swelling and histological evaluation. Interleukin-17 production in lymph node cells was determined by an enzyme-linked immunosorbent assay (ELISA). Foxp3 expression in lymph node cells and the phenotypes of splenic dendritic cells were examined by fluorescence-activated cell sorting (FACS). Bone marrow-derived dendritic cells (BM-DC) were generated with granulocyte macrophage colony-stimulating factor. The effects of trichostatin A on cell surface molecules, cytokine production, indoleamine 2,3-dioxygenase (IDO) expression and T cell stimulatory capacity were examined by FACS, ELISA, quantitative real-time polymerase chain reaction and Western blot, and the allo-mixed lymphocyte reaction, respectively. Results: Trichostatin A, when administered before the onset of arthritis, prevented SKG mice from getting arthritis. Trichostatin A treatment also showed therapeutic effects on arthritis in SKG mice, when it was administered after the onset of