Cranberry proanthocyanidins inhibit MMP production and activity.
Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in periodontal tissue destruction. Our aim was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on: (i) the production of various MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), and (ii) the catalytic activity of recombinant MMP-1 and MMP-9. The effects of AC-PACs on the expression of 5 protein kinases and the activity of nuclear factor-kappa B (NF-kappaB) p65 in macrophages stimulated with LPS were also monitored. Our results indicated that AC-PACs inhibited the production of MMPs in a concentration-dependent manner. Furthermore, the catalytic activity of MMP-1 and MMP-9 was also inhibited. The inhibition of MMP production was associated with reduced phosphorylation of key intracellular kinases and the inhibition of NF-kappaB p65 activity. AC-PACs thus show potential for the development of novel host-modulating strategies to inhibit MMP-mediated tissue destruction during periodontitis.
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Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, 2420 Rue de Terrasse, Quebec City, QC, Canada G1V 0A6.
Howell
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Grenier
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D016976:Aggregatibacter actinomycetemcomitans; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008070:Lipopolysaccharides; D008264:Macrophages / Q000201:enzymology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010518:Periodontitis / Q000201:enzymology*; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D029799:Vaccinium macrocarpon
D008070:Lipopolysaccharides; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D010936:Plant Extracts; D044945:Proanthocyanidins; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D011494:Protein Kinases; D020782:Matrix Metalloproteinases