Activation of transcription factor NF-kappa B in human synovial cells in response to tumor necrosis factor alpha

Objective. To examine whether nuclear factor kappa B (NF-kappa B) is activated in cultured synovial cells in response to tumor necrosis factor alpha (TNF alpha and to investigate the correlation between NF-kappa 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 reverse transcriptase polymerase chain reaction and transient expression assay using human immunodeficiency virus-long terminal repeat chloramphenicol acetyltransferase. Proliferative activity was determined by measurement of H-3-thymidine incorporation. Results. Stimulation of synovial cells with TNF alpha activated NF-kappa B and subsequent transcription of several genes. Treatment of synovial cells with N-acetyl-L-cysteine (NAC), an antioxidant agent, inhibited TNF alpha-induced NF-kappa B activation and transcription. Moreover, NAC also inhibited synovial cell proliferation induced by TNF alpha. Conclusion. Our results suggest that NF-kappa B plays a pivotal role in synovial cell activation by TNF alpha. Thus, suppression of NF-kappa B could be a potential therapeutic modality for synovitis such as that of rheumatoid arthritis.