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Cranberry proanthocyanidins inhibit MMP production and activity
V D La1, A B Howell, D Grenier
1Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, 2420 Rue de Terrasse, Quebec City, QC, Canada G1V 0A6.
Abstract:
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.
Insights
A-type cranberry proanthocyanidins (AC-PACs) inhibit matrix metalloproteinases (MMPs) linked to periodontal disease. These compounds reduce MMP production and activity, offering potential for new treatments against tissue destruction.
Area of Science:
- Periodontology
- Immunology
- Natural Products Chemistry
Background:
- Matrix metalloproteinases (MMPs) are key mediators of periodontal tissue destruction, often produced by inflammatory cells in response to pathogens.
- Understanding host-modulating strategies is crucial for managing periodontitis and preventing tissue damage.
Purpose of the Study:
- To investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on MMP production and activity in macrophages stimulated by Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS).
- To explore the impact of AC-PACs on intracellular signaling pathways, including protein kinases and nuclear factor-kappa B (NF-kappaB) p65 activity.
Main Methods:
- Human monocyte-derived macrophages were stimulated with LPS to induce MMP production.
- The effects of varying concentrations of AC-PACs on MMP production, catalytic activity (MMP-1, MMP-9), protein kinase phosphorylation, and NF-kappaB p65 activity were assessed.
Main Results:
- AC-PACs demonstrated a concentration-dependent inhibition of MMP production by macrophages.
- The catalytic activity of recombinant MMP-1 and MMP-9 was significantly inhibited by AC-PACs.
- Inhibition of MMPs correlated with reduced phosphorylation of key intracellular kinases and decreased NF-kappaB p65 activity.
Conclusions:
- AC-PACs effectively inhibit MMP production and activity, suggesting a role in mitigating periodontal tissue destruction.
- The findings highlight the potential of AC-PACs as a novel host-modulating agent for periodontitis treatment.
- AC-PACs may offer a therapeutic strategy by targeting MMP-mediated pathways involved in inflammatory tissue damage.
