Activated Ras modifies the proliferative response of rheumatoid synovial cells to TNF-alpha and TGF-alpha

Inflamm Res. 2001 Dec;50(12):592-7. doi: 10.1007/PL00000239.


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.

Conclusion: Ras modulates the proliferative response of RSF to TNF-alpha and TGF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Arthritis, Rheumatoid / pathology*
  • Blotting, Northern
  • Cell Division / genetics
  • Cell Survival / drug effects
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Flavonoids / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / physiology
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / physiology*
  • Signal Transduction / physiology
  • Stimulation, Chemical
  • Synovial Membrane / cytology
  • Synovial Membrane / pathology*
  • Transforming Growth Factor alpha / pharmacology*
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Enzyme Inhibitors
  • Flavonoids
  • Transforming Growth Factor alpha
  • Tumor Necrosis Factor-alpha
  • Mitogen-Activated Protein Kinases
  • Oncogene Protein p21(ras)
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one