title: Activated Ras modifies the proliferative response of rheumatoid synovial cells to TNF-alpha and TGF-alpha.
abstract: OBJECTIVE
  To study the role of the Ras/mitogen-activated protein kinase (MAPK) pathway in the proliferative response of rheumatoid synovial fibroblast (RSF) to tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-alpha.
  
  
  METHODS
  V-Ki-ras gene was introduced into RSF using a retrovirus and the proliferative response of these cells to TNF-alpha or TGF-alpha was estimated by measuring the uptake of 3H-thymidine. The effect of a mitogen-activated protein kinase kinase (MEK) inhibitor, PD98059, was also investigated.
  
  
  RESULTS
  Consistent with previous reports, TNF-alpha and TGF-alpha stimulated the proliferation of RSF. When the v-Ki-ras gene was expressed, the basal growth rate of these cells was increased, but their growth was suppressed by TNF-alpha or TGF-alpha. The latter effect was abolished when the cells were exposed to a relatively low concentration of PD98059.
  
  
  CONCLUSIONS
  Ras modulates the proliferative response of RSF to TNF-alpha and TGF-alpha.
authors.affiliation: Department of Microbiology, Kitasato University, School of Medicine, Sagamihara, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kitasato
authors.forename: M
authors.initials: M
authors.lastname: Noda
authors.forename: T
authors.initials: T
authors.lastname: Akahoshi
authors.forename: R
authors.initials: R
authors.lastname: Okamoto
authors.forename: T
authors.initials: T
authors.lastname: Koshino
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: S
authors.initials: S
authors.lastname: Kawai
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D015152:Blotting, Northern; D002455:Cell Division / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D013583:Synovial Membrane / Q000166:cytology / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D015689:Oncogene Protein p21(ras); C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one