tailieunhanh - Báo cáo y học: "c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis. | Paniagua et al. Arthritis Research Therapy 2010 12 R32 http content 12 1 R32 RESEARCH ARTICLE Open Access c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis Ricardo T Paniagua Anna Chang Melissa M Mariano Emily A Stein Qian Wang Tamsin M Lindstrom Orr Sharpe1 2 Claire Roscow1 2 Peggy P Ho3 David M Lee4 William H Robinson1 2 Abstract Introduction Tyrosine kinases are key mediators of multiple signaling pathways implicated in rheumatoid arthritis RA . We previously demonstrated that imatinib mesylate-a Food and Drug Administration FDA -approved antineoplastic drug that potently inhibits the tyrosine kinases Abl c-Kit platelet-derived growth factor receptor PDGFR and c-Fms-ameliorates murine autoimmune arthritis. However which of the imatinib-targeted kinases is the principal culprit in disease pathogenesis remains unknown. Here we examine the role of c-Fms in autoimmune arthritis. Methods We tested the therapeutic efficacy of orally administered imatinib or GW2580 a small molecule that specifically inhibits c-Fms in three mouse models of RA collagen-induced arthritis CIA anti-collagen antibody-induced arthritis CAIA and K BxN serum transfer-induced arthritis K BxN . Efficacy was evaluated by visual scoring of arthritis severity paw thickness measurements and histological analysis. We assessed the in vivo effects of imatinib and GW2580 on macrophage infiltration of synovial joints in CIA and their in vitro effects on macrophage and osteoclast differentiation and on osteoclast-mediated bone resorption. Further we determined the effects of imatinib and GW2580 on the ability of macrophage colony-stimulating factor M-CSF the ligand for c-Fms to prime bone marrow-derived macrophages to produce tumor necrosis factor TNF upon subsequent Fc receptor ligation. Finally we measured M-CSF levels in synovial fluid from patients with RA osteoarthritis OA or psoriatic .