DIRECT EVIDENCE OF HIGH DNA-BINDING ACTIVITY OF TRANSCRIPTION FACTOR AP-1 IN RHEUMATOID-ARTHRITIS SYNOVIUM

Objective. To investigate the possible activation of transcription fac tor AP-1 in rheumatoid arthritis (RA) and its involvement in the patho genesis of RA. Methods. Synovial tissues and peripheral blood samples were obtained from 25 patients with RA and 5 patients with osteoarthri tis (OA) during arthroplasty and synovectomy. The synovial tissue was digested with collagenase and separated into adherent and nonadherent cells by plastic-adhesion methods, Nuclear extracts obtained from each sample were examined by electrophoretic mobility shift assay to deter mine the DNA binding activity of AP-1. The expression of c-fos and c-j un messenger RNA (mRNA) was examined by in situ reverse transcription assay. Results. A markedly high DNA binding activity of AP-1 was detec ted in the synovial tissues of RA patients, while virtually no activit y or only a little activity was observed in OA patients, Following sep aration of adherent and nonadherent cells, the AP-1 activity was mainl y detected in adherent cells, which consisted of synovial cells and ma crophages. However, the activity was significantly higher in the monon uclear cells infiltrating into RA synovium than in RA peripheral blood mononuclear cells, The high DNA binding activity of AP-1 in RA correl ated with the expression of c-fos and c-jun mRNA in situ. Furthermore, AP-1 binding activity also correlated with disease activity. Conclusi on. In RA synovium, AP-1 DNA binding activity was constitutively up-re gulated. These findings suggest that AP-1 may play an important role i n the pathogenesis of RA, including synoival hyperplasia and abnormal immune responses.