Independent effects of interleukin 1 on proteoglycan synthesis and proteoglycan breakdown of bovine articular cartilage in vitro.
We studied the effects of human recombinant interleukin-1 beta on proteoglycan metabolism of bovine articular cartilage in organ culture. IL-1 was more potent in inhibiting synthesis (IC50 4 ng/mL) than in stimulating breakdown of proteoglycans (EC50 200 ng/mL). Inhibition of proteoglycan synthesis began to plateau earlier (2 days) than stimulation of proteoglycan release (4 days). Both effects could be neutralized with a polyclonal anti-IL-1 beta antibody; however, higher antibody titers were required to block IL-1 effects on proteoglycan synthesis than to neutralize those on proteoglycan release. Chloroquine, but not hydrocortisone, blocked IL-1-mediated proteoglycan breakdown. Both drugs, however, augmented IL-1-induced inhibition of proteoglycan synthesis. Our data suggest that the effects of IL-1 on articular cartilage proteoglycan synthesis and proteoglycan breakdown can be regulated independently.
Neidel
J
J
Articular Cartilage Research Laboratory, University Department of Orthopaedics, Köln, Germany.
Zeidler
U
U
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002417:Cattle; D002738:Chloroquine / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000276:immunology / Q000494:pharmacology*; D007700:Kinetics; D011509:Proteoglycans / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism
D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D013431:Sulfates; D002738:Chloroquine; D006854:Hydrocortisone