Cycloheximide inhibits the induction of collagenase mRNA in chondrocytes exposed to synovial factors or recombinant interleukin-1.
Synoviocytes secrete "chondrocyte activating factors" (CAF) which, like recombinant interleukin-1 (IL-1), induce the synthesis of collagenase by cultures of articular chondrocytes. Enzyme synthesis is preceded by the appearance of collagenase mRNA some 3-5 hours after exposure of the chondrocytes to CAF or IL-1. Cycloheximide (CX) inhibits the appearance of this message in a dose-dependent manner. At a concentration of 5 micrograms/ml inhibition by CX is completely reversible, with superinduction being observed in certain experiments. Identification of the newly synthesised proteins which are required for collagenase mRNA induction would greatly advance our understanding of collagenase gene expression.
Lin
C W
CW
Ferguson Laboratory for Orthopaedic Research, University of Pittsburgh School of Medicine, PA.
Georgescu
H I
HI
Phillips
S L
SL
Evans
C H
CH
D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology; D003513:Cycloheximide / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003012:Microbial Collagenase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011817:Rabbits; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013582:Synovial Fluid / Q000502:physiology*
D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003513:Cycloheximide; D003012:Microbial Collagenase