title: Activation of transcription factor NF-kappa B in human synovial cells in response to tumor necrosis factor alpha.
abstract: 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.
authors.affiliation: University School of Medicine, Kawasaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujisawa
authors.forename: H
authors.initials: H
authors.lastname: Aono
authors.forename: T
authors.initials: T
authors.lastname: Hasunuma
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Mita
authors.forename: K
authors.initials: K
authors.lastname: Nishioka
mesh_terms: 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*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine