Activation of transcription factor NF‐κB in human synovial cells in response to tumor necrosis factor α

Abstract

Objective. To examine whether nuclear factor κB (NF-κB) is activated in cultured synovial cells in response to tumor necrosis factor α (TNFα) and to investigate the correlation between NF-κB activation and synovial cell proliferation. Methods. Activation of NF-κB was detected by electrophoretic mobility shift assay. The transcription of several NF-κB–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 ³H-thymidine incorporation. Results. Stimulation of synovial cells with TNFα activated NF-κB and subsequent transcription of several genes. Treatment of synovial cells with N-acetyl-L-cysteine (NAC), an antioxidant agent, inhibited TNFα-induced NF-κB activation and transcription. Moreover, NAC also inhibited synovial cell proliferation induced by TNFα. Conclusion. Our results suggest that NF-κB plays a pivotal role in synovial cell activation by TNFα. Thus, suppression of NF-κB could be a potential therapeutic modality for synovitis such as that of rheumatoid arthritis.