Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts

Longstanding Remission of Adult Onset Still’s Disease Under Imatinib Therapy in a Patient with Chronic Myelogenous Leukemia: Figure 1.

“…Recent reports have shown that imatinib proved beneficial in patients with various autoimmune disorders, including RA, systemic scleroderma, pulmonary arterial hypertension, lupus nephritis, ankylosing spondylitis, psoriasis, and Crohn's disease [1][2][3][4][5] . Consistent with the clinical findings, in vitro studies demonstrated that imatinib can inhibit multiple signaling pathways implicated in the pathogenesis of various autoimmune disorders, including T-cell proliferation, macrophage c-fms activation and cytokine production, c-Kit-mediated mast-cell release of TNF-α and IL-6, and synovial fibroblast PDGF receptor signaling and proliferation 3,[7][8][9][10] . AOSD is a systemic inflammatory disease that includes the participation of various cytokines such as IL-1, IL-6, IL-18, TNF-α, macrophage colony-stimulating factor, PDGF, and interferon-γ.…”

Platelet-Derived Growth Factor-β Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing

“…This is in agreement with a recent analysis of synovial fibroblasts showing that imatinib blocked proliferation without affecting apoptosis. 34 Imatinib treatment resulted in a reduction in the number of ␣-SMA-expressing myofibroblasts and reduced expression of ED-A FN, which is crucial for myofibroblast formation. 35 After 3 days, ␣-SMA immunostaining, denoting the presence of myofibroblasts, was present in control tissue but absent in treated tissue.…”

Interleukin‐17–positive mast cells contribute to synovial inflammation in spondylarthritis

“…It needs, however, to be emphasized that imatinib mesylate blocks other factors in addition to c-Kit, such as other tyrosine kinases, in particular the macrophage colonystimulating factor receptor c-Fms, which is expressed on macrophage subtypes, and the PDGF receptor, which is expressed on synovial fibroblasts (48,49). Therefore, it is possible that the effects observed in the ex vivo synovial tissue cultures may not be solely due to modulation of mast cells.…”