OBJECTIVE: To examine whether nuclear factor kappaB (NF-kappaB) is activated in cultured synovial cells in response to tumor necrosis factor alpha (TNFalpha) and to investigate the correlation between NF-kappaB activation and synovial cell proliferation. METHODS: Activation of NF-kappaB was detected by electrophoretic mobility shift assay. The transcription of several NF-kappaB-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 TNFalpha activated NF-kappaB and subsequent transcription of several genes. Treatment of synovial cells with N-acetyl-L-cysteine (NAC), an antioxidant agent, inhibited TNFalpha-induced NF-kappaB activation and transcription. Moreover, NAC also inhibited synovial cell proliferation induced by TNFalpha. CONCLUSION: Our results suggest that NF-kappaB plays a pivotal role in synovial cell activation by TNFalpha. Thus, suppression of NF-kappaB could be a potential therapeutic modality for synovitis such as that of rheumatoid arthritis.
OBJECTIVE: To examine whether nuclear factor kappaB (NF-kappaB) is activated in cultured synovial cells in response to tumor necrosis factor alpha (TNFalpha) and to investigate the correlation between NF-kappaB activation and synovial cell proliferation. METHODS: Activation of NF-kappaB was detected by electrophoretic mobility shift assay. The transcription of several NF-kappaB-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 TNFalpha activated NF-kappaB and subsequent transcription of several genes. Treatment of synovial cells with N-acetyl-L-cysteine (NAC), an antioxidant agent, inhibited TNFalpha-induced NF-kappaB activation and transcription. Moreover, NAC also inhibited synovial cell proliferation induced by TNFalpha. CONCLUSION: Our results suggest that NF-kappaB plays a pivotal role in synovial cell activation by TNFalpha. Thus, suppression of NF-kappaB could be a potential therapeutic modality for synovitis such as that of rheumatoid arthritis.
Authors: S Wakisaka; N Suzuki; M Takeno; Y Takeba; H Nagafuchi; N Saito; H Hashimoto; T Tomita; T Ochi; T Sakane Journal: Ann Rheum Dis Date: 1998-08 Impact factor: 19.103
Authors: Robby D Bowles; Brian A Mata; Richard D Bell; Timothy K Mwangi; Janet L Huebner; Virginia B Kraus; Lori A Setton Journal: Arthritis Rheumatol Date: 2014-03 Impact factor: 10.995