Transforming growth factor-beta is a potent inhibitor of IL-1 induced protease activity and cartilage proteoglycan degradation.
Treatment of chondrocytes in culture with interleukin-1 results in the production of neutral proteases that cause the degradation of the large aggregating proteoglycan. TGF-beta is a pleiotropic growth factor that has been shown to induce differentiation of cartilage and, in some cases, was able to inhibit the IL-1-dependent processes. In this report, we examined whether TGF-beta could block the IL-1 induced catabolic effects on chondrocytes. After treatment with IL-1 beta (30 ng/ml), rabbit articular chondrocytes produced approximately 2 units of neutral protease activity. Under identical conditions, TGF-beta 1 alone did not induce any protease activity. However, a combination of IL-1 and TGF-beta resulted in a dramatic reduction in the level of protease activity. The inhibitory effect of TGF-beta was also observed at the level of proteoglycan incorporation into the extracellular matrix. The IL-1 treated chondrocytes failed to incorporate proteoglycans into their extracellular matrix. However, addition of TGF-beta in the presence of IL-1 resulted in partial reversal towards a normal extracellular matrix. These studies indicate that TGF-beta can block and at least partially inhibit the catabolic effects of IL-1 on chondrocytes.
Chandrasekhar
S
S
Department of Connective Tissue and Monoclonal Antibody Research, Lilly Corporate Center, Indianapolis, IN 46285.
Harvey
A K
AK
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D002808:Chondroitin Lyases / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism; D004357:Drug Synergism; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013431:Sulfates / Q000378:metabolism; D015291:Transforming Growth Factors / Q000494:pharmacology*
D007375:Interleukin-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D013431:Sulfates; D005346:Fibroblast Growth Factors; D015291:Transforming Growth Factors; D002809:Chondroitin Sulfates; D008666:Metalloendopeptidases; D002808:Chondroitin Lyases