Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) is induced in rabbit articular chondrocytes by cotreatment with interleukin 1 beta and a protein kinase C activator.
The synthesis of an 88-kDa gelatinolytic enzyme, identified as a zymogen of matrix metalloproteinase (proMMP)-9, was induced in the primary culture of rabbit articular chondrocytes by cotreatment with recombinant interleukin 1 beta (rIL-1 beta) and the protein kinase C (PKC) agonists, phorbol 12,13-dibutyrate (PDBu) or mezerein. Negligible 88-kDa gelatinolytic activity was produced by unstimulated cells or cells treated with a PKC activator alone at concentrations up to 100 ng/ml, and only a modest induction occurred with rIL-1 beta alone at concentrations of 1-100 ng/ml. However, when these cells were treated with a PKC activator in the presence of IL-1 beta (1 ng/ml), induction was striking, with enzymic activity detectable at a concentration as low as 1 ng/ml of mezerein or 10 ng/ml of PDBu. Rabbit chondrocytes in culture constitutively produced the zymogen of MMP-2 (proMMP-2) and its production was not altered by treatment with IL-1 beta or PKC agonists alone or in combination. Recombinant tumor necrosis factor alpha (rTNF alpha) did not substitute for IL-1 beta in inducing proMMP-9 in the presence of PKC activators, nor was the combination of IL-1 beta or TNF alpha alone effective. These data indicate that rabbit articular chondrocytes have a potential to synthesize and secrete proMMP-9 under certain biological and pathological conditions but that the expression of proMMP-9 is differently regulated from that of other MMPs.
Ogata
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Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66103.
Pratta
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MA
Nagase
H
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Arner
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EC
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured / Q000187:drug effects; D004224:Diterpenes; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D004792:Enzyme Precursors; D005786:Gene Expression Regulation; D007375:Interleukin-1 / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9; D003012:Microbial Collagenase / Q000096:biosynthesis*; D010703:Phorbol Esters / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology
D004224:Diterpenes; D004792:Enzyme Precursors; D007375:Interleukin-1; D010703:Phorbol Esters; D011994:Recombinant Proteins; D013729:Terpenes; C011309:mezerein; D003012:Microbial Collagenase; D020780:Matrix Metalloproteinase 9