Upregulation of enzymatic activity by interleukin-1 in osteoarthritis.
Osteoarthritis is a slow progressive disease characterized by destruction of the articular cartilage. The degradation of extracellular matrix components is mainly mediated by a family of enzymes, the metalloproteinases (MMPs), which are active at neutral pH. Interleukin-1 (IL-1) is a small peptide, active in autocrine and paracrine fashions. In vitro IL-1 increases the production of MMPs and inhibits the synthesis of collagen type II and proteoglycans. Its role in osteoarthritis is based on several findings: IL-1 is detectable in the synovial fluid and in the cartilage matrix of osteoarthritic joints; in vivo its deleterious actions can be reproduced by intra-articular injection of recombinant IL-1; biochemical changes observed in the cartilage matrix from osteoarthritic joints resemble those induced in vitro by IL-1; finally, antagonists of IL-1 are capable in vivo of preventing or at least diminishing the degradation of cartilage matrix components in several models of experimental arthritis. Interleukin-1 appears to be a main factor mediating cartilage matrix destruction. However, its role in human osteoarthritis, although highly probable, remains to be determined.
Chevalier
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Rheumatology Department, Hôpital Henri-Mondor, Créteil, France.
D002358:Cartilage, Articular / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology* / Q000502:physiology; D008666:Metalloendopeptidases / Q000378:metabolism*; D010003:Osteoarthritis / Q000201:enzymology* / Q000503:physiopathology; D015854:Up-Regulation
D007375:Interleukin-1; D008666:Metalloendopeptidases