Activation of rabbit articular chondrocytes by recombinant human cytokines.
Treatment of rabbit articular chondrocytes with 0.5-5 units/ml of recombinant human interleukin-1 (IL-1) induced phospholipase A2 (PLA2) activation, prostaglandin E2 (PGE2) biosynthesis and latent neutral protease secretion by these cells. When normalized on the basis of thymocyte costimulatory activity, the beta (pI 7) form of recombinant IL-1 was about 5-fold more potent than the alpha (pI 5) species, although the maximum response induced by either IL-1 form was similar. Recombinant murine IL-1 was also a potent dose dependent activator of chondrocyte arachidonate metabolism and protease secretion. In contrast to IL-1, neither IL-2 nor tumor necrosis factor alpha (TNF alpha) activated PLA2, PGE2, or neutral protease secretion in these cells and neither of these cytokines inhibited the chondrocyte metabolic response to IL-1. These results provide unequivocal evidence that IL-1 is a potent activator of chondrocyte arachidonate metabolism and hydrolytic protease secretion. That all 3 recombinant IL-1 molecules stimulate chondrocytes and yet share limited sequence homology suggests that an amino acid sequence common to all 3 species is required for chondrocyte activation.
Gilman
S C
SC
Immunopharmacology Subdivision, Wyeth laboratories Inc., Philadelphia, PA 19101.
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects*; D015232:Dinoprostone; D010450:Endopeptidases / Q000378:metabolism*; D007375:Interleukin-1 / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage; D015260:Neprilysin; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011458:Prostaglandins E / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D007375:Interleukin-1; D007376:Interleukin-2; D011458:Prostaglandins E; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010450:Endopeptidases; D015260:Neprilysin; D015232:Dinoprostone