Synthesis and regulation of keratinocyte collagenase.
We have recently demonstrated that human keratinocytes synthesize and secrete procollagenase and tissue inhibitor of metalloproteinases (TIMP) in culture. We have examined the response of keratinocyte collagenase production to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), interleukin-1, extracellular matrix proteins and phagocytosis. Collagenase production in keratinocytes was markedly stimulated by TPA and paralleled the morphologic changes induced by the phorbol ester. Synthesis of collagenase increased six- to 34-fold with TPA, whereas the level of TIMP rose only three-fold. Interleukin-1 did not stimulate collagenase production by the keratinocytes, in contrast to its effect on cultured fibroblasts. When keratinocytes were plated on type I or type IV collagen, they synthesized increased amounts of collagenase compared with cells cultured on laminin or in the absence of matrix. TIMP synthesis was not increased by collagen. Finally, phagocytosis of latex beads did not augment collagenase production by the keratinocytes.
Petersen
M J
MJ
Division of Dermatology, University of Utah, Salt Lake City.
Woodley
D T
DT
Stricklin
G P
GP
O'Keefe
E J
EJ
D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology*; D010587:Phagocytosis; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007375:Interleukin-1; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D013755:Tetradecanoylphorbol Acetate