In vitro effect of platelet-derived growth factor on fibroproliferation and effect of cytokine antagonists

Abstract

Platelet-derived growth factor (PDGF) stimulates fibroblast proliferation and increases collagen synthesis. Fibroproliferation, as assessed by tritiated thymidine uptake, was significantly stimulated by platelet-derived growth factor (8 ng/ml). Several drugs including dexamethasone (1 nM-20 microM), cysteamine (1.3-65 mM), N-acetylcysteine (0.6-15 mM), glutathione (1 microM-0.1 mM), glutathione peroxidase (0.1-1 Unit/ml), pentoxifylline (60 microM-36 mM), colchicine (0.025-250 nM) and aurothioglucose (1.15-23 microM) were assessed in the fibroproliferation assay for their ability to block the fibroproliferative effect of platelet-derived growth factor. Dexamethasone and aurothioglucose did not affect PDGF-stimulated fibroproliferation, while pentoxifylline, colchicine, cysteamine and N-acetylcysteine effectively reduced fibroproliferation stimulated by PDGF. The effect of pentoxifylline on PDGF stimulated fibroproliferation was compared to trapidil, theophylline and adenosine to assess mechanism of action. All four methylxanthines effectively inhibited PDGF stimulated fibroproliferation. Pentoxifylline was as effective as trapidil (IC50 = 129 microM and 141 microM, respectively), but pentoxifylline was more potent than theophylline (IC50 = 688 microM) and pentoxifylline was not as potent as adenosine (IC50 = 19 microM) in reducing PDGF-stimulated fibroproliferation.