The protective effects of histone deacetylases inhibitor TSA on the mice model of rheumatoid arthritis

Objective: To investigate the effects of trichostatin A (TSA) on the mice model of collagen induced arthritis(CIA). Methods: Mice model of rheumatoid arthritis(RA) was induced in DBA/1 mice with type II collagen. Paws were scored for histological severity of arthritis. The severity of inflammation of mouse joint was evaluated by histological examination. Real-time PCR was used to determine the cytokine mRNA expression. Cytokine production was measured by ELISA from serum, spleen cell culture or dendritic cell and T cell co-culture supernatant. T cell proliferation was examined by MTT method. Results: TSA can significantly suppress the severity of the arthritis in CIA. IFN-γ was elevated in CIA mice, but was inhibited significantly by TSA introduced either at the same time with immunization or at the onset of manifestation of arthritis. Collagen specific T cell proliferation was significantly suppressed by introduction of TSA. Increased level of IL-4 by T cells was observed in TSA treated group compared to that of control group. Conclusion: IL-4 level was increased and played a critical role in the protective effects of TSA in CIA. TSA suppresses the progress of CIA by regulates the balance of Th1/Th2 differentiation.