Platelet-derived growth factor potentiates cellular responses of articular chondrocytes to interleukin-1

Recombinant human interleukin-1 alpha (IL-1 alpha) induced a time-dependent (0-72 hours) and concentration-dependent (0.01-10 ng/ml) production of metalloproteinases (collagenase, gelatinase, stromelysin) and prostaglandin E2 (PGE2) in rabbit articular chondrocytes (RAC). Exposure of RAC to recombinant human platelet-derived growth factor homodimer BB (PDGF-BB; 2-200 ng/ml) in the presence of stimulatory and substimulatory concentrations of IL-1 alpha resulted in a marked augmentation of metalloproteinase and PGE2 production. PDGF-BB exerted no agonist effects on RAC responsiveness. PDGF-BB up-regulated the number of IL-1 receptors per chondrocyte but had no effect on receptor affinity. Cycloheximide and actinomycin D caused a concentration-dependent suppression of the PDGF-BB-mediated potentiation of radiolabeled IL-1 alpha binding to RAC and cell responsiveness to IL-1 alpha. Similarly, IL-1 increased the number of PDGF receptors on RAC without changing receptor affinity. These data are discussed within the context of cytokine-growth factor interactions as components of the pathogenesis of arthritic diseases.