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


CONCLUSIONS
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.
Fujisawa
K
K
University School of Medicine, Kawasaki, Japan.
Aono
H
H
Hasunuma
T
T
Yamamoto
K
K
Mita
S
S
Nishioka
K
K
D000111:Acetylcysteine / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine