Imatinib mesylate inhibits proliferation of rheumatoid synovial fibroblast‐like cells and phosphorylation of Gab adapter proteins activated by platelet‐derived growth factor

Summary Receptors for platelet‐derived growth factor (PDGF) are abundantly expressed on synovial fibroblast‐like (SFL) cells from patients with rheumatoid arthritis (RA), and stimulation with PDGF enhances both the anchorage‐dependent and ‐independent growth of RA–SFL cells. To elucidate the molecul...

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Bibliographic Details
Published in:Clinical and experimental immunology 2006-05, Vol.144 (2), p.335-341
Main Authors: Kameda, H., Ishigami, H., Suzuki, M., Abe, T., Takeuchi, T.
Format: Article
Language:English
Subjects:
adapter proteins
Adaptor Proteins, Signal Transducing - immunology
Animal Studies
arthritis
Arthritis - immunology
Arthritis, Rheumatoid - immunology
Benzamides
Biological and medical sciences
Cell Division - immunology
Cells, Cultured
Fibroblasts - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
growth factors
Humans
Imatinib Mesylate
Immunopathology
Medical sciences
Osteoarthritis - immunology
Phosphorylation
Piperazines - immunology
Platelet-Derived Growth Factor - immunology
Protein Kinase Inhibitors - immunology
Pyrimidines - immunology
Receptors, Platelet-Derived Growth Factor - immunology
signal transduction
Signal Transduction - immunology
Synovial Membrane - immunology
Synovial Membrane - pathology
Tyrosine - metabolism
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Summary:Summary Receptors for platelet‐derived growth factor (PDGF) are abundantly expressed on synovial fibroblast‐like (SFL) cells from patients with rheumatoid arthritis (RA), and stimulation with PDGF enhances both the anchorage‐dependent and ‐independent growth of RA–SFL cells. To elucidate the molecular mechanisms responsible for the excessive growth of RA–SFL cells and to seek a novel molecular‐targeting therapy for RA, we examined the expression of adapter proteins and the effect of the specific inhibition of PDGF receptor activation by imatinib mesylate. Cultured SFL cells were used in the present study after 2–5 passages. The anchorage‐dependent and ‐independent growth patterns of the SFL cells were evaluated using a tetrazolium‐based assay and colony formation in 0·3% agar, respectively. Adapter proteins Gab1 and Gab2 were expressed in RA–SFL cells, and both proteins were rapidly (
ISSN:0009-9104
1365-2249
DOI:10.1111/j.1365-2249.2006.03067.x