Involvement of the 92-kDa gelatinase (matrix metalloproteinase-9) in the ceramide-mediated inhibition of human keratinocyte growth.
Triggering the ceramide pathway by exogenous treatment with neutral sphingomyelinase (Smase) inhibited human keratinocyte growth rate, while having no influence on cell apoptosis. Increasing the ceramide content of keratinocytes with Smase (100 U/ml) or C6-ceramide (1 microM) enhanced matrix metalloproteinase (MMP)-9 production. On the contrary, levels of MMP-2 secretion were unchanged. The inhibition of keratinocyte growth rate induced by ceramide could be annihilated by a peptide hydroxamate MMP inhibitor or an MMP-9 blocking antibody. In addition, inhibiting MMP-9 activity in control keratinocyte culture was found to stimulate keratinocyte proliferation. These data suggest a pivotal function of MMP-9 in the control of keratinocyte growth.
UPRESA 6021 CNRS IFR 53 Biomolécules, Faculté de Médecine et Faculté des Sciences, Université de Reims-Champagne Ardenne, Reims, France.
N
N
Buisson-Legendre
P
P
Bernard
H
H
Bobichon
H
H
Emonard
C
C
Schneider
F X
FX
Maquart
B
B
Haye
W
W
Hornebeck
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology*; D017364:Collagenases / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D013997:Time Factors
D000906:Antibodies; D002518:Ceramides; D061965:Matrix Metalloproteinase Inhibitors; C064769:N-acetylsphingosine; D013876:Thiophenes; C101954:N-caproylsphingosine; D010649:Phenylalanine; D004815:Epidermal Growth Factor; C080985:batimastat; D013108:Sphingomyelin Phosphodiesterase; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013110:Sphingosine