title: Effect of glycated albumin and cranberry components on interleukin-6 and matrix metalloproteinase-3 production by human gingival fibroblasts.
abstract: OBJECTIVE
  Gingival fibroblasts have the potential to participate in periodontal inflammation and breakdown, producing interleukin (IL)-6 and matrix metalloproteinase (MMP)-3. Advanced glycation end products (AGEs), formed during diabetic hyperglycemia, might aggravate periodontal inflammation. The cranberry contains anti-inflammatory polyphenols, which inhibit proinflammatory activities of lipopolysaccharide (LPS)- and IL-1β-stimulated human cells. Little is known of its effects on gingival fibroblast IL-6 or MMP-3 production stimulated by AGEs. The objectives were to determine cranberry effects on IL-6 and MMP-3 production by gingival fibroblasts exposed to the representative AGE, glycated human serum albumin (G-HSA), or LPS ± G-HSA.
  
  
  METHODS
  Cranberry high molecular weight non-dialyzable material (NDM), was derived from cranberry juice. Normal human gingival fibroblasts were incubated with G-HSA or normal HSA or Porphyromonas gingivalis LPS (1 μg/mL) ± G-HSA, in the presence or absence of preincubation with NDM. IL-6 and MMP-3 were measured by enzyme-linked immunosorbent assay. Data were analyzed using one-way analysis of variance and Scheffe's F procedure.
  
  
  RESULTS
  IL-6 production was stimulated by G-HSA or LPS (p < 0.01), which was inhibited in both cases by NDM (p < 0.002). [G-HSA+LPS] synergistically stimulated IL-6 production (p < 0.0001), which was inhibited by NDM. MMP-3 levels were not stimulated by G-HSA but were decreased by LPS (p < 0.02). [G-HSA+LPS] increased MMP-3 production significantly, vs. LPS (p = 0.0005). NDM inhibited MMP-3 levels in the presence of G-HSA or LPS, and in the presence of [G-HSA+LPS] (p < 0.0001).
  
  
  CONCLUSIONS
  G-HSA ± LPS may have differential effects on IL-6 and MMP-3 production by human gingival fibroblasts, but both are inhibited by NDM. The study suggests that cranberry phenols may be useful in regulating the host response and perhaps treating periodontitis in patients with poorly controlled diabetes.
authors.affiliation: College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Tipton
authors.affiliation: College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Hatten
authors.affiliation: College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Babu
authors.affiliation: College of Dentistry, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Bioscience Research, University of Tennessee Health Science Center, Memphis, TN, USA.|College of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.|Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: M Kh
authors.initials: MKh
authors.lastname: Dabbous
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts; D005881:Gingiva; D006801:Humans; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D020781:Matrix Metalloproteinase 1; D016966:Porphyromonas gingivalis
chemical_list: C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: cranberry; cytokine(s); diabetes; fibroblasts; matrix metalloproteinase(s); periodontitis