TY - JOUR
T1 - The synovial activation of chondrocytes
T2 - evidence for complex cytokine interactions involving a possible novel factor
AU - Bandara, G.
AU - Lin, C. W.
AU - Georgescu, H. I.
AU - Evans, C. H.
N1 - Funding Information:
We are very gratefutl o the individualsn amedi n the Materialsa ndM ethodss ectionf or providingth eeDNA probes, antibodiesa nd IL-I receptora ntagonispt ro-tein. In addition, we thank Ms. Carmen Bryant of California BiotechnologIyn c. who kindly assayedc on-ditioned media for the presenceo f bFGF. We also thank L. Melntyref or assistancwe ith the bioassayfso r IL-1, TNF-a and IL-6. Mrs. Lou Duerringw onderfully typed the manuscript. Supportedb y N.I.H. grant No. AR 36891 and the Western PennsylvaniCa hapterof the Arthritis Foundation.
PY - 1992/4/7
Y1 - 1992/4/7
N2 - Preparations of lapine synovial 'chondrocy-e activating factors' (CAF) were analyzed for the presence of individual cytokines which modulate the production of neutral metalloproteinases (NMPs) and prostaglandin E2 (PGE2) by articular chondrocytes. A combination of different biochemical analyses suggested that synovial fibroblasts secrete IL-1α, which activated chondrocytes directly, bFGF,which potentiated the activity of IL-1, and TGF-β 1, which produced a bivalent response. TGF-β 1 suppressed NMP synthesis by chondrocytes, but enhanced PGE2 synthesis. The IL-1 receptor antagonist protein (IRAP) eliminated chondrocyte activation by IL-1, but only partially inhibited activation by CAF. Thus, CAF may contain a cytokine in addition to IL-1 which activates chondrocytes. This putative additional factor was more thermosensitive than IL-1, and had an apparent molecular weight of approx. 20 000 when estimated by size exclusion chromatography. Of a variety of purified cytokines tested for their ability to induce NMPs in chondrocytes, only IL-1 was active. This favours the possibility that the activity which resists suppression by IRAP reflects the presence of a novel cytokine.
AB - Preparations of lapine synovial 'chondrocy-e activating factors' (CAF) were analyzed for the presence of individual cytokines which modulate the production of neutral metalloproteinases (NMPs) and prostaglandin E2 (PGE2) by articular chondrocytes. A combination of different biochemical analyses suggested that synovial fibroblasts secrete IL-1α, which activated chondrocytes directly, bFGF,which potentiated the activity of IL-1, and TGF-β 1, which produced a bivalent response. TGF-β 1 suppressed NMP synthesis by chondrocytes, but enhanced PGE2 synthesis. The IL-1 receptor antagonist protein (IRAP) eliminated chondrocyte activation by IL-1, but only partially inhibited activation by CAF. Thus, CAF may contain a cytokine in addition to IL-1 which activates chondrocytes. This putative additional factor was more thermosensitive than IL-1, and had an apparent molecular weight of approx. 20 000 when estimated by size exclusion chromatography. Of a variety of purified cytokines tested for their ability to induce NMPs in chondrocytes, only IL-1 was active. This favours the possibility that the activity which resists suppression by IRAP reflects the presence of a novel cytokine.
KW - Chondrocyte activating factor
KW - Cytokine
KW - Interleukin-1
KW - Neutral metalloproteinase
KW - Receptor antagonist
KW - Synoviocyte
UR - http://www.scopus.com/inward/record.url?scp=0026504886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026504886&partnerID=8YFLogxK
U2 - 10.1016/0167-4889(92)90192-E
DO - 10.1016/0167-4889(92)90192-E
M3 - Article
C2 - 1558854
AN - SCOPUS:0026504886
SN - 0167-4889
VL - 1134
SP - 309
EP - 318
JO - BBA - Molecular Cell Research
JF - BBA - Molecular Cell Research
IS - 3
ER -