Grape seed extract suppresses lipopolysaccharide-induced matrix metalloproteinase (MMP) secretion by macrophages and inhibits human MMP-1 and -9 activities.
BACKGROUND
Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to Gram-negative periodontopathogens play a major role in the tissue destruction observed during periodontitis, a disease that affects tooth-supporting structures. In this study, we investigated the effect of grape seed extract (GSE) on MMP secretion by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS) and on the activity of human recombinant MMP-1 and -9.


METHODS
Macrophages were treated with various concentrations of GSE prior to being stimulated with A. actinomycetemcomitans LPS. The secretion of MMPs and activation of nuclear factor-kappa B (NF-kappaB) p65 and activator protein-1 (AP-1) were assessed by enzyme-linked immunosorbent assay (ELISA). The effect of GSE on the catalytic activity of human recombinant MMP-1 and -9 was tested using fluorogenic assays.


RESULTS
GSE inhibited the secretion of MMP-1, -3, -7, -8, -9, and -13 by LPS-stimulated macrophages in a concentration-dependent manner. The suppression of MMP secretion was associated with inhibition of NF-kappaB p65 and AP-1 activation. Also, GSE dose-dependently inhibited the activity of MMP-1 and -9.


CONCLUSIONS
The present study suggests that GSE may be potentially used in the development of novel host-modulating strategies for the treatment of MMP-mediated disorders such as periodontitis.
La
Vu Dang
VD
Research Group in Oral Ecology, Faculty of Dentistry, Laval University, Quebec City, QC, Canada.
Bergeron
Chantal
C
Gafner
Stefan
S
Grenier
Daniel
D
D016976:Aggregatibacter actinomycetemcomitans / Q000502:physiology*; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D056604:Grape Seed Extract / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects; D011994:Recombinant Proteins; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors
D000975:Antioxidants; D056604:Grape Seed Extract; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1