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.
Conclusion:
Ras modulates the proliferative response of RSF to TNF-alpha and TGF-alpha.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Arthritis, Rheumatoid / pathology*
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Blotting, Northern
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Cell Division / genetics
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Cell Survival / drug effects
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Cells, Cultured
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Enzyme Inhibitors / pharmacology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Flavonoids / pharmacology
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Gene Expression Regulation / drug effects
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Humans
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / physiology
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Oncogene Protein p21(ras) / genetics
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Oncogene Protein p21(ras) / physiology*
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Signal Transduction / physiology
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Stimulation, Chemical
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Synovial Membrane / cytology
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Synovial Membrane / pathology*
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Transforming Growth Factor alpha / pharmacology*
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Enzyme Inhibitors
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Flavonoids
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Transforming Growth Factor alpha
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Tumor Necrosis Factor-alpha
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Mitogen-Activated Protein Kinases
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Oncogene Protein p21(ras)
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one