Signal transduction blockade with imatinib mesylate prevents and treats autoimmune arthritis (B76)
| Autor: | Ricardo Paniagua, Orr Sharpe, Peggy Ho, Steven Chan, Anna Chang, Beren Tomooka, David Lee, Mark Genovese, Paul Utz, Lawrence Steinman, William Robinson |
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| Rok vydání: | 2007 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 178:LB16-LB16 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | For over two decades researchers have speculated on the potential use of kinase inhibitors to treat autoimmune diseases. To date, investigations of kinase inhibitors have been largely limited by low therapeutic indices that result in unacceptable toxicity profiles. We show that imatinib mesylate, a tyrosine kinase inhibitor FDA-approved to treat chronic myeloid leukemia and gastrointestinal stromal tumors, has the potential to provide benefit for autoimmune diseases such as rheumatoid arthritis (RA). We demonstrate that imatinib, at a dose equivalent to 200–400mg/day in humans, prevents murine autoimmune arthritis and treats established disease. We further show that submicromolar imatinib concentrations inhibit tyrosine kinases and cellular responses that are central to RA pathogenesis, including PDGF-mediated proliferation of fibroblast-like synoviocytes, c-Fms activation and macrophage production of TNF-alpha, c-Kit-mediated mast cell release of proinflammatory cytokines, and B cell immunoglobulin production. Inhibition of tyrosine kinase pathways by imatinib represents a potent and promising therapeutic approach to treat RA and other autoimmune diseases. |
| Databáze: | OpenAIRE |
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