Proteoglycan- and collagen-degrading enzymes from human interleukin 1-stimulated chondrocytes from several species: proteoglycanase and collagenase inhibitors as potentially new disease-modifying antiarthritic agents.
Human IL-1-stimulated chondrocytes derived from rabbit, bovine, and human articular cartilage produce proteoglycan- and collagen-degrading enzymes. These studies demonstrate that the biological activity of IL-1 is not species specific. Several thiol, carboxyalkyl, and hydroxamic acid peptide inhibitors showed differential effects. The thiols were equipotent inhibitors of both the collagen- and proteoglycan-degrading enzymes whereas the carboxyalkyls appear to inhibit solely the proteoglycan-degrading enzyme(s). The hydroxamic acid peptides, the most potent inhibitors, appear to be more active against the proteoglycan-degrading enzymes. These synthetic inhibitors of proteoglycan- and/or collagen-degrading enzymes may represent a new class of disease-modifying antiarthritic agents.
D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002417:Cattle; D003094:Collagen / Q000378:metabolism*; D010450:Endopeptidases; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008666:Metalloendopeptidases; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits
D007375:Interleukin-1; D011480:Protease Inhibitors; D011509:Proteoglycans; D003094:Collagen; D010450:Endopeptidases; C022474:proteoglycan-degrading metalloendopeptidases; D008666:Metalloendopeptidases; D003012:Microbial Collagenase