Trichostatin A inhibits dendritic cell maturation through down-regulating NF-κ B (p65) pathway.

ABSTRACT

BACKGROUND: Recent evidence suggested that histone deacetylase inhibitor (HDACi) could inhibit dendritic cell (DC) maturation. However, the mechanism is unclear. Here, we aimed to study whether Trichostatin A (TSA), the most widely studied HDACi, inhibits the maturation of DCs by down-regulating NF-κB (p65) pathway. METHODS AND RESULTS: Mouse bone marrow-derived DCs were cultured. Lipopolysaccharide (LPS) was applied as stimulation for maturation. Triptolide (TTL) was applied as p65 inhibitor. Microphotography and flow cytometry showed that TSA and p65 inhibitor separately inhibited the maturation of DCs stimulated by LPS from the aspects of cell morphology and cell phenotype. Mixed lymphocyte reaction test and ELISA showed that TSA and p65 inhibitor synergistically inhibited the proliferation of T lymphocytes stimulated by DCs, reduced the secretion of pro-inflammatory cytokine IL-12 and elevated the secretion of anti-inflammatory cytokine IL-10. Western blot and RT-qPCR showed that TSA down-regulated the expression of phosphorylated IκBα, phosphorylated-p65, Ikkß and Ikkγ, suggesting TSA down-regulates NF-κB (p65) pathway. CONCLUSIONS: TSA inhibits DC maturation through down-regulating NF-κB (p65) pathway.