Independent effects of interleukin-1 on proteoglycan breakdown, proteoglycan synthesis, and prostaglandin E2 release from cartilage in organ culture.
Exposure of bovine nasal cartilage in culture to interleukin-1 (IL-1) leads to a time- and concentration-dependent stimulation of proteoglycan breakdown and prostaglandin E2 (PGE2) release, and to inhibition of proteoglycan synthesis. The threshold levels of IL-1 required for initiating these effects were different, and IL-1 was 10 times more potent in inhibiting synthesis than in stimulating breakdown of proteoglycan. Kinetic studies indicated that the effects on proteoglycan metabolism occurred earlier (16-24 hours) than those for PGE2 release (48 hours). Selective effects were observed with inhibitors. Nonsteroidal antiinflammatory drugs blocked PGE2 production in response to IL-1, but had no effect on proteoglycan metabolism, and the antiarthritic drugs that blocked IL-1-stimulated breakdown augmented the inhibition of proteoglycan synthesis. We suggest that the effects of IL-1 on proteoglycan breakdown, proteoglycan synthesis, and PGE2 release are mediated by independent post-receptor mechanisms.
Arner
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Medical Products Department, E. I. Du Pont de Nemours and Company, Inc., Wilmington, Delaware 19880-0400.
Pratta
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MA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D015232:Dinoprostone