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

Clinical and Experimental Immunology
H KamedaT Takeuchi

Abstract

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 (< 1 min) tyrosine-phosphorylated after the stimulation of RA-SFL cells with 10 ng/ml of PDGF and, to a lesser extent, after stimulation with 100 ng/ml of epidermal growth factor (EGF). The inhibition of PDGF receptor tyrosine kinase activation by 1 microM or less of imatinib mesylate specifically suppressed the PDGF-dependent, but not EGF-dependent, tyrosi...Continue Reading

References

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Citations

Jun 6, 2009·Nature Reviews. Rheumatology·Christina D'Aura SwansonWilliam H Robinson
Jan 8, 2008·Arthritis Research & Therapy·Ulf Müller-LadnerThomas Pap
May 1, 2009·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Hideto Kameda
Oct 14, 2008·International Immunopharmacology·Antonio G Tristano
Jun 29, 2007·La Revue de médecine interne·A TaïebF-X Mahon
Jul 3, 2007·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Hideto Kameda
Jan 7, 2010·Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases·Timothy SullivanJohn F Deeken
Mar 23, 2010·Current Opinion in Rheumatology·Zoltán SzekaneczAlisa E Koch
Aug 29, 2012·Oncogene·Y YangJ T Celebi
Jan 25, 2008·Dermatology : International Journal for Clinical and Investigative Dermatology·A SoriaA Taïeb
Oct 30, 2009·Autoimmunity·Zoltán SzekaneczAlisa E Koch
Aug 2, 2012·Molecular and Cellular Biochemistry·Xiaofang ZhuSongshu Meng

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