Systemic delivery of C II TA siRNA reduces disease severity in collagen-induced arthritis

Abstract

Objective To examine the therapeutic effect of C Ⅱ TA inhibition in collagen-induced arthritis(CIA),using a delivery system tailored to target C ⅡTA gene by small interfering RNA (siRNA).Methods Mice with collagen-induced arthritis were injected intravenously with C Ⅱ TA siRNA.The clinical score was monitored for up to 4 weeks after treatment.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.T cell proliferation was examined by MTT method.Results IFN-γ and IL-17 were elevated in CIA mice,but were iuhibited significantly by C Ⅱ TA siRNA either prevention or intervention of autoimmune arthritis.Collagen specific T cell proliferation was significantly suppressed.Increased level of IL-4 by T cells was observed in C Ⅱ TA siRNA treated group compared with that of control group.Conclusion Our findings indicate that systemic RNAi-mediated C Ⅱ TA gene silencing is effective in the treatment of CIA and regulateds the balance of Th1/Th2 differentiation. Key words: Rheumatoid arthritis; siRNA; Dendritic cell; IFN-γ; IL-4; IL-7