THE EFFECTS OF IL-1 ON MITOGEN-ACTIVATED PROTEIN-KINASES IN RABBIT ARTICULAR CHONDROCYTES

IL-1-activated chondrocytes express a large number of genes which cont ribute to cartilage degradation. The signaling pathways activated in r esponse to IL-1 in these cells are not well-defined. We examined the e ffects of IL-1 and other stimuli on the mitogen activated protein kina se (MAPK) pathways in rabbit articular chondrocytes. We demonstrate th at IL-1 activates three MAPKs, ERK, JNK and p38, in a time and dose-de pendent manner. Activation is maximal by 15 minutes and returns to bas eline levels by 1 hour. Maximal activation of ERK and p38 occurs with 1 ng/ml IL-1 whereas activation of JNK requires 10-fold higher levels. In contrast to IL-1, the PKC activator, PDBu preferentially activates ERK while TNF alpha preferentially activates JNK. LPS and TGF beta fa il to stimulate any of the kinases examined. These results suggest tha t activation of the various MAPK pathways is important in the response of chondrocytes to IL-1, cytokines and growth factors. (C) 1997 Acade mic Press