Inhibition of cartilage proteoglycan synthesis by interleukin I.
We have investigated the mechanism of inhibition of cartilage proteoglycan by interleukin 1. Proteoglycan synthesis was inhibited using lower doses of interleukin 1 than those required to cause cartilage resorption. There was no significant effect on DNA or total protein synthesis. Gel electrophoresis showed a direct inhibitory effect on core protein synthesis while pulse-chase experiments using radiolabelled sulphate showed no alteration in the rate of intracellular transport and secretion of completed proteoglycan. Chondrocytes incubated with cycloheximide showed a first-order decrease in rate of uptake of radiolabelled sulphate (t1/2 = 25 mins) but interleukin 1 induced inhibition showed a delay of at least 1 hr, consistent with a requirement to deplete intracellular pools of protein before effects on post-translational events could be observed. Foetal and neonatal cartilage responded to the cytokine in a similar way to adult cartilage.
Benton
H P
HP
Strangeways Research Laboratory, Worts Causeway, Cambridge, U.K.
Tyler
J A
JA
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002356:Cartilage / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D005333:Fetus; D006025:Glycosaminoglycans / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D011509:Proteoglycans / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013552:Swine
D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D003513:Cycloheximide