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Effects of cranberry components on human aggressive periodontitis gingival fibroblasts
Author(s) -
Tipton D. A.,
Babu J. P.,
Dabbous M. Kh.
Publication year - 2013
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/jre.12023
Subject(s) - lipopolysaccharide , fibroblast , chemistry , viability assay , periodontitis , interleukin , microbiology and biotechnology , apoptosis , biochemistry , immunology , biology , in vitro , cytokine , medicine
Background and Objective Aggressive periodontitis ( A g P ) causes rapid periodontal breakdown involving A g P gingival fibroblast production of cytokines [i.e. interleukin ( IL )‐6, a bone metabolism regulator], and matrix metalloproteinase ( MMP )‐3. Lipopolysaccharide upregulates fibroblast IL ‐6 and MMP ‐3, via transcription factors (i.e. NF ‐κ B ). Cranberry ( V accinium macrocarpon ) inhibits lipopolysaccharide‐stimulated macrophage and normal gingival fibroblast activities, but little is known of its effects on A g P fibroblasts. Objectives of this study are to use A g P fibroblasts, to determine cytotoxicity of cranberry components or periodontopathogen ( F usobacterium nucleatum, P orphyromonas gingivalis ) lipopolysaccharide ± cranberry components, and effects of cranberry components on lipopolysaccharide‐stimulated NF ‐κ B activation and IL ‐6 and MMP ‐3 production.Material and Methods A g P fibroblasts were incubated ≤ 6 d with high molecular weight non‐dialyzable material ( NDM ) (derived from cranberry juice (1–500 μg/mL) or lipopolysaccharide (1 μg/mL) ± NDM . Membrane damage and viability were assessed by enzyme activity released into cell supernatants and activity of a mitochondrial enzyme, respectively. Secreted IL ‐6 and MMP ‐3 were measured by ELISA . NF ‐κ B p65 was measured via binding to an oligonucleotide containing the NF ‐κ B consensus site. Data were analyzed using analysis of variance and S cheffe's F procedure for post hoc comparisons.Results Short‐term exposure to NDM , or lipopolysaccharide ± NDM caused no membrane damage. NDM ( ≤ 100 μg/mL) or lipopolysaccharide ± NDM had no effect on viability ≤ 7 d exposure. NDM (50 μg/mL) inhibited lipopolysaccharide‐stimulated p65 ( P ≤ 0.003) and constitutive or lipopolysaccharide‐stimulated MMP ‐3 ( P ≤ 0.02). NDM increased A g P fibroblast constitutive or lipopolysaccharide‐stimulated IL ‐6 ( P ≤ 0.0001), but inhibited normal human gingival fibroblast IL ‐6 ( P ≤ 0.01).Conclusion Lack of toxicity of low NDM concentrations, and its inhibition of NF ‐κ B and MMP ‐3, suggest that cranberry components may regulate A g P fibroblast inflammatory responses. Distinct effects of NDM on A g P and gingival fibroblast production of IL ‐6 (which can have both positive and negative effects on bone metabolism) may reflect phenotypic differences in IL ‐6 regulation in the two cell types.