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Activated Ras modifies the proliferative response of rheumatoid synovial cells to TNF-alpha and TGF-alpha
H Kitasato1, M Noda, T Akahoshi
1Department of Microbiology, Kitasato University, School of Medicine, Sagamihara, Japan.
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.