Recombinant human interleukin-1 inhibits plasminogen activator inhibitor-1 (PAI-1) production by human articular cartilage and chondrocytes.

Human articular cartilage and chondrocyte monolayers in culture constitutively produced plasminogen activator inhibitor-1 (PAI-1) protein and mRNA, as assessed by a specific enzyme-linked immunosorbent assay and Northern blotting analysis, respectively. Recombinant human interleukin-1 (IL-1) invoked a dose-dependent inhibition of PAI-1 production in both cartilage and chondrocyte cultures. The inhibitory effect of IL-1 was observed between 2-8h after addition of the cytokine, while the optimal dose was between 10-100U/ml IL-1 alpha (57-570pM IL-1 alpha). Results obtained by Northern analysis of chondrocyte total RNA reflected those found for the PAI-1 antigen, namely, that nontreated chondrocytes showed PAI-1 mRNA which was reduced by IL-1 treatment. To our knowledge, this is the first report where IL-1 has been found to inhibit PAI-1 expression. Since IL-1 has been shown before to cause human cartilage destruction and a correlated change in plasminogen activator activity, it could be that a concomitant reduction in PAI-1 levels by IL-1 may be significant in the control of these changes in cartilage.