The inhibition of interleukin 1-stimulated cartilage proteoglycan degradation by cysteine endopeptidase inactivators.
Cysteine endopeptidase inactivators were tested as inhibitors of interleukin 1-stimulated proteoglycan release from bovine nasal septum cartilage explants. Hydrophilic inactivators showed no inhibition at concentrations up to 100 microM. In contrast, lipophilic inactivators gave significant inhibition, which was both reversible and specific. No effects on interleukin 1 signal transduction were detected, but rates of proteoglycan synthesis were apparently increased. Our results suggest that one or more of the lysosomal cathepsins B, L and S mediate cytokine-stimulated proteoglycan degradation, and the turnover of newly synthesized proteoglycan, but that effective inhibitors must pass through membranes.
Buttle
D J
DJ
Strangeways Research Laboratory, Worts Causeway, Cambridge, U.K.
Saklatvala
J
J
Barrett
A J
AJ
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002403:Cathepsins / Q000378:metabolism; D002417:Cattle; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D009300:Nasal Septum / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
D002403:Cathepsins; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D015232:Dinoprostone; D007375:Interleukin-1; D015850:Interleukin-6; D007930:Leucine; D011509:Proteoglycans; D000093242:Interleukin-6 Inhibitors; C032425:N-(N-(3-carboxyoxirane-2-carbonyl)leucyl)isoamylamine; C108192:aloxistatin