Cytokine modulation of plasminogen activator inhibitor-1 (PAI-1) production by human articular cartilage and chondrocytes. Down-regulation by tumor necrosis factor α and up-regulation by transforming growth factor-β and basic fibroblast growth factor

Abstract

Recombinant human cytokines were examined for their effects on plasminogen activator inhibitor-1 (PAI-1) production by human articular cartilage and chondrocyte monolayer cultures. Cartilage and chondrocytes were cultured with and without added cytokines and the conditioned media assayed for PAI-1 by a specific enzyme-linked immunosorbent assay, and mRNA levels determined by Northern blot analysis. Tumor necrosis factor α (TNFα) reduced, and transforming growth factor-β (TGF-β) and basic fibroblast growth factor (bFGF) increased, the levels of PAI-1 antigen and mRNA in the culture fluids and cell extracts, respectively. The effects of TNFα and TGF-β on PAI-1 antigen levels were both time- an..