Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts.
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.
Sandler
Charlotta
C
Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Finland.
Joutsiniemi
Saima
S
Lindstedt
Ken A
KA
Juutilainen
Timo
T
Kovanen
Petri T
PT
Eklund
Kari K
KK
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*
D001549:Benzamides; D004338:Drug Combinations; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate