Differential regulation of metalloprotease steady-state mRNA levels by IL-1 and FGF in rabbit articular chondrocytes.
The expression of collagenase and stromelysin is believed to be coordinately regulated. In this report however, we provide evidence that suggests subtle differences may exist in the early events of the induction of these enzymes. Rabbit articular chondrocytes treated with interleukin-1, either alone or in combination with fibroblast growth factor, accumulated steady-state mRNA levels for both the enzymes, with the latter treatment more effective in inducing greater levels and within a shorter time. Further, the induction of the enzymes by either protocol was blocked by cycloheximide co-treatment. Cycloheximide added 1 h post-stimulation with interleukin-1 + fibroblast growth factor failed to block stromelysin mRNA expression, but was able to block collagenase steady-state mRNA levels. Transforming growth factor-beta, another inhibitor of metallprotease induction, showed no such differential activity. The results suggest that collagenase and stromelysin may have subtle variations in their induction pathways. Our studies further show that the enzyme induction by interleukin-1 alone or in combination with fibroblast growth factor occurs through different, but related mechanisms.
Chandrasekhar
S
S
Skeletal Diseases Research, Lilly Research Laboratories, Indianapolis, IN 46285.
Harvey
A K
AK
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002469:Cell Separation; D003513:Cycloheximide / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006133:Growth Substances / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000187:drug effects / Q000378:metabolism*; D003012:Microbial Collagenase / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D016212:Transforming Growth Factor beta
D006133:Growth Substances; D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D003513:Cycloheximide; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D003012:Microbial Collagenase