Inhibition of host extracellular matrix destructive enzyme production and activity by a high-molecular-weight cranberry fraction.
OBJECTIVE
Periodontal diseases are a group of inflammatory disorders that are initiated by specific gram-negative bacteria and lead to connective tissue destruction. Proteolytic enzymes, including matrix metalloproteinases (MMPs) and elastase, produced by resident and inflammatory cells in response to periodontopathogens and their products, play a major role in gingival tissue destruction. The aim of this study was to investigate the effect of a high-molecular-weight fraction prepared from cranberry juice concentrate on MMP-3, MMP-9 and elastase activities, as well as on MMP production by human cells stimulated with lipopolysaccharide of Actinobacillus actinomycetemcomitans.


METHODS
MMP-3 and MMP-9 production by gingival fibroblasts and macrophages treated with the cranberry fraction and then stimulated with lipopolysaccharide was measured by enzyme-linked immunosorbent assay. MMP-3, MMP-9 and elastase activities in the presence of the cranberry fraction were evaluated using colorimetric or fluorogenic substrates. The changes in expression and phosphorylation state of fibroblast intracellular signaling proteins induced by A. actinomycetemcomitans lipopolysaccharide and the cranberry fraction were characterized by antibody microarrays.


RESULTS
The lipopolysaccharide-induced MMP-3 and MMP-9 responses of fibroblasts and macrophages were inhibited in a dose-dependent manner by the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. MMP-3, MMP-9 and elastase activities were also efficiently inhibited by the cranberry fraction, even when it was used at low concentrations.


CONCLUSIONS
These results suggest that cranberry compounds offer promising perspectives for the development of novel host-modulating strategies for an adjunctive treatment of periodontitis.
Bodet
C
C
Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec, Canada.
Chandad
F
F
Grenier
D
D
D016976:Aggregatibacter actinomycetemcomitans; D005109:Extracellular Matrix / Q000201:enzymology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D061965:Matrix Metalloproteinase Inhibitors; D008970:Molecular Weight; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology; D040081:Protein Array Analysis; D020298:U937 Cells / Q000187:drug effects / Q000201:enzymology; D029799:Vaccinium macrocarpon
D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D044945:Proanthocyanidins; D019272:Leukocyte Elastase