Objective. To identify and investigate the kinetic binding properties of interleukin-1 receptors (IL-lR), and examine the abilities of the-2 IL-1 isoforms to stimulate metalloprotease synthesis, in normal and osteoarthritic (OA) chondrocytes.Methods. Receptor affinity and density were determined using radioligand binding experiments and flow cytometry. Immunocytochemical analysis and affinity cross-linking studies were performed for characterization of IL-1R.Results. While no difference in receptor affinity Factors such as IL-2, interferon-y, tumor necrosis factor a, and bovine insulin did not compete with IL-1p. By covalent ligand cross-linking and electrophoretic analysis, only type I IL-lR, a protein of 80 kd, was detected on chondrocytes. By immunocytochemical analysis, IL-1R was identified at the cell membrane level, in both normal and OA chondrocytes. The presence of nuclear staining was also observed, but only in OA chondrocytes. Recombinant human IL-1 (a and p) induced the secretion of stromelysin and collagenase in a dose-dependent manner. The IL-1 concentration required for half-maximal metalloprotease stimulation was 3-4 times lower in OA chondrocytes than in normal cells.
_____Conclusion. These results indicate that OA chondrocytes have a higher sensitivity to the stimulation of metalloprotease synthesis by IL-1 than do normal cells. This could be related to the increased levels of IL-1R expressed in the OA cells. The implications of these findings with regard to the possible roles of IL-1 and IL-1R in the pathogenesis of OA are discussed.Erosion of articular cartilage in osteoarthritis (OA) is probably mediated by proteolytic degradation of extracellular matrix macromolecules. Metalloproteases are believed to be the primary enzyme systems
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