Transfection of double gene co-expressing adenovirus vector into arthritis rats

BACKGROUND: Abnormal activation of lymphocytes and nuclear factor κB-dependent non-specific inflammation are two major manifestations of joint damage in rheumatoid arthritis. Co-stimulatory signal CD40/CD40L is the dominant co-stimulatory factor in the recognition and activation of T cells. IκBα effectively inhibits nuclear factor κB pathway, prevent the inflammation in the central link, and suppress the damage caused by inflammatory factor in the synovial tissue. OBJECTIVE: To investigate the therapeutic effect of double gene co-expressing adenovirus vector on arthritis based on an arthritis model rat transfected by CD40LIg-IRES2-IκBα co-expressing adenovirus vector. METHODS: The pAdCD40LIg-IRES2-IκBα co-expressing adenovirus vector was established. Arthritic model was established through multi-subcutaneous injections of complete Freund's adjuvant of type collagen ll (1 g/L) into Wistar rats. Then 20 arthritic rats were divided into two groups: untreated group and transfection group, receiving an injection of saline and pAdCD40LIg-IRES2-IκBα adenovirus vector to distal joint cavity of limbs, respectively. RESULTS AND CONCLUSION: At 14 days post-transfection, compared with the untreated group, the mean arthritis index score, the CD40L expression of lymphocytes in synovial fluid, the nuclear factor-κB p65 expression in synovial tissue, and levels of interleukin-2, interleukin-6, tumor necrosis factor-a, matrix metalloproteinase-3 and matrix metalloproteinase-9 in synovial fluid of rats in transfection group were significantly lower than those in untreated group. Focal transfection of the CD40LIg-IκBα co-expression adenovirus vector can effectively inhibit arthritic symptoms, and reduce the expressions of inflammatory cytokine in synovial fluid and inflammatory molecule in synovial tissue of arthritic rats, which shows good therapeutic effect.