Protein kinase C and chondrocyte activation.
We have begun to examine the role of protein kinase C (PKC) in chondrocyte activation by interleukin-1 (IL-1) in search of a possible signal transduction mechanism. Untreated chondrocytes synthesised little or no collagenase or gelatinase and only modest amounts of prostaglandin E2 (PGE2), while IL-1 induced considerable amounts of these. An activator of PKC, phorbol myristate acetate (PMA), alone did not influence the synthesis of the metalloproteinases to any great degree, but enhanced PGE2 production. Sphingosine and staurosporin, inhibitors of PKC, each eliminated the synergistic effect of PMA upon enzyme induction by high doses (10 U/ml) of IL-1, but failed to influence enzyme induction by this dose of IL-1 alone. However, a low dose (1 U/ml) of IL-1 in combination with these inhibitors was synergistic upon enzyme induction. Although these inhibitors reduced the synthesis of PGE2 in response to PMA, synthesis of PGE2 in response to both doses of IL-1 was greatly enhanced by the inhibitors. PMA, but not IL-1, enhanced the phosphorylation of an 80 K protein which is characteristic of PKC activity in certain types of cells. From these data, we conclude that PKC is unlikely to be involved in the induction of neutral metalloproteinases by IL-1, although once induction has occurred, PKC may modulate this effect. PKC may also act as regulator of PGE2 synthesis, although this requires further investigation.
Hulkower
K I
KI
Ferguson Laboratory for Orthopaedic Research, University of Pittsburgh School of Medicine, PA 15261.
Georgescu
H I
HI
Evans
C H
CH
D000818:Animals; D001345:Autoradiography; D002358:Cartilage, Articular / Q000166:cytology* / Q000201:enzymology; D015232:Dinoprostone / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D013110:Sphingosine / Q000494:pharmacology
D010761:Phosphorus Radioisotopes; D011493:Protein Kinase C; D015232:Dinoprostone; D013110:Sphingosine