Aggressive periodontitis (AP) causes rapid
periodontal breakdown involving AP gingival fibroblast production of cytokines [i.e.
interleukin (IL)-6, a bone metabolism regulator], and matrix metalloproteinase
(MMP)-3. Lipopolysaccharide (LPS) upregulates fibroblast IL-6 and MMP-3, via
transcription factors (i.e. NF-kB). Cranberry (Vaccinium
macrocarpon) inhibits LPS-stimulated macrophage and normal gingival (GN)
fibroblast activities. Little is known of its effects on AP fibroblasts. Objectives:
using AP fibroblasts, determine cytotoxicity of cranberry components or
periodontopathogen (Fusobacterium nucleatum, Porphyromonas gingivalis)
LPS ± cranberry components, and effects on NF-kB activation and
IL-6 and MMP-3 production. Methods: AP fibroblasts were incubated ≤6 d with
NDM (high molecular weight non-dialyzable material derived from cranberry juice;
1-500 µg/ml) or LPS (1 µg/ml) ± NDM. Membrane damage and viability were
assessed by enzyme activity released into cell supernatants and activity of a
mitochondrial enzyme, respectively. IL-6 and MMP-3 were measured by ELISA. NF-kB
p65 was measured via binding to an oligonucleotide containing the NF-kB
consensus site. Data were analyzed using ANOVA and Scheffe's F procedure for
post hoc comparisons. Results: Short-term exposure to NDM, or LPS ± NDM caused
no membrane damage. NDM (≤ 100 µg/ml) or LPS ± NDM had no effect on
viability ≤ 7d exposure. NDM (50 µg/ml) inhibited LPS-stimulated p65
(p≤0.003) and constitutive or LPS-stimulated MMP-3 (p≤0.02). NDM
increased AP fibroblast constitutive or LPS-stimulated IL-6 (p≤0.0001),
but inhibited GN fibroblast IL-6 (p≤0.04). Conclusion: Lack of toxicity
of low NDM concentrations to AP fibroblasts in vitro, and its inhibition of NF-kB
and MMP-3, suggest that cranberry components may regulate oral fibroblast
inflammatory responses and may be useful in prevention/treatment of gingivitis/periodontitis.
Differences in NDM effects on AP and GN fibroblast production of IL-6 (which
can have both positive and negative effects on bone metabolism) may reflect
phenotypic differences and differing roles in bone metabolism. (Supported by The
Cranberry Institute).