ACTIVATION OF TRANSCRIPTION FACTOR NF-KAPPA-B IN HUMAN SYNOVIAL-CELLSIN RESPONSE TO TUMOR-NECROSIS-FACTOR-ALPHA

Objective. To examine whether nuclear factor kappa B (NF-kappa B) is a ctivated in cultured synovial cells in response to tumor necrosis fact or alpha (TNF alpha and to investigate the correlation between NF-kapp a B activation and synovial cell proliferation. Methods. Activation of NF-kappa B was detected by electrophoretic mobility shift assay. The transcription of several NF-kappa B-dependent genes was evaluated by r everse transcriptase polymerase chain reaction and transient expressio n assay using human immunodeficiency virus-long terminal repeat chlora mphenicol acetyltransferase. Proliferative activity was determined by measurement of H-3-thymidine incorporation. Results. Stimulation of sy novial cells with TNF alpha activated NF-kappa B and subsequent transc ription of several genes. Treatment of synovial cells with N-acetyl-L- cysteine (NAC), an antioxidant agent, inhibited TNF alpha-induced NF-k appa B activation and transcription. Moreover, NAC also inhibited syno vial cell proliferation induced by TNF alpha. Conclusion. Our results suggest that NF-kappa B plays a pivotal role in synovial cell activati on by TNF alpha. Thus, suppression of NF-kappa B could be a potential therapeutic modality for synovitis such as that of rheumatoid arthriti s.