Effects Of Histone Deacetylase Inhibitor Fulinuo On Expression Of CCL17 And CD4 + CD25 + T Cell Proliferation And Differentiation In Mouse Bone Marrow Derived Dendritic Cells

BackgroundAtherosclerosis, the common pathophysiologic process for coronary artery disease and stroke, is considered as a comprehensive inflammatory reaction. Dendritic cell is a very important but less understood population which shows up in both innate immune response and adaptive immune response. Chemokine C-C motif ligand 17, or thymus and activation regulated chemokine, is secreted by dendritic cells and considered as a pro-inflammatory chemokine regulating CD4+ T cell activation and Treg homeostasis. Vorinostat, a non-specific histone deacetylase inhibitor, is approved by FDA for cutaneous T cell lymphoma.MethodDendritic cells are induced by GM-CSF and IL-4 from bone marrow precursors and peripheral splenic cells are collected. CD11c+ DCs and CD4+ T cells are purified from specific Microbeads from Mitenyl. Treated by vorinostat with a concentration of 0.05uM、0.1uM、0.5uM、1.0uM, cells and supernatant are collected for further experiment. Real-Time quantification PCR and ELISA are performed. Incubate cells with anti-CD4-FITC and anti-CD25-PE and then analyzed by flow cytometry. Results a. Ccl17 expression is significantly suppressed when incubation time prolonged. b. CCL17 is accumulated during very early stage and turned up to be no difference between 12h/24h/36h/72h groups. c. The mRNA and protein level of ccl17 in the supernatant is significantly suppressed by vorinostat. d. The efficacy of CD4+CD25+T cells differentiated from CD4+T cells is enhanced by dendritic cells. However, vorinostat is observed to be invalid in emerging Treg proliferation.Conclusion Ccl17 expression by dendritic cells is suppressed by vorinostat when concentration is 0.05～1.0uM. CD4+CD25+ Treg induction from T cells is emerged by dendritic cells regardless of vorinostat.