title: Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts.
abstract: Synovial fibroblast is the key cell type in the growth of the pathological synovial tissue in arthritis. Here, we show that platelet-derived growth factor (PDGF) is a potent mitogen for synovial fibroblasts isolated from patients with rheumatoid arthritis. Inhibition of PDGF-receptor signalling by imatinib mesylate (1muM) completely abrogated the PDGF-stimulated proliferation and inhibited approximately 70% of serum-stimulated proliferation of synovial fibroblasts. Similar extent of inhibition was observed when PDGF was neutralized with anti-PDGF antibodies, suggesting that imatinib mesylate does not inhibit pathways other than those mediated by PDGF-receptors. No signs of apoptosis were detected in synovial fibroblasts cultured in the presence of imatinib. These results suggest that imatinib mesylate specifically inhibits PDGF-stimulated proliferation of synovial fibroblasts, and that inhibition of PDGF-receptors could represent a feasible target for novel antirheumatic therapies.
authors.affiliation: Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Finland.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Sandler
authors.forename: Saima
authors.initials: S
authors.lastname: Joutsiniemi
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Timo
authors.initials: T
authors.lastname: Juutilainen
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Kari K
authors.initials: KK
authors.lastname: Eklund
mesh_terms: D001172:Arthritis, Rheumatoid / Q000473:pathology* / Q000503:physiopathology; D001549:Benzamides; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000008:administration & dosage*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage*; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology*
chemical_list: D001549:Benzamides; D004338:Drug Combinations; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate