title: Inhibition of interleukin-17-stimulated interleukin-6 and -8 production by cranberry components in human gingival fibroblasts and epithelial cells.
abstract: OBJECTIVE
  Gingival epithelial cells and fibroblasts participate in periodontal inflammation and destruction, producing interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8. IL-17, a product of T-helper 17 cells, may play a role in periodontitis by stimulating cytokine production by gingival cells. The cranberry (Vaccinium macrocarpon) is rich in polyphenols, particularly proanthocyanidins, which have antioxidant and other beneficial properties. Cranberry components inhibit pro-inflammatory activities of lipopolysaccharide-stimulated human macrophages, gingival fibroblasts, and epithelial cells, but little is known of its effects on IL-17-stimulated cytokine production. The objectives were to determine the effects of IL-17 ± cranberry components on IL-6 and IL-8 production by human gingival epithelial cells and fibroblasts.
  
  
  METHODS
  Cranberry high molecular weight non-dialyzable material (NDM), which is rich in proanthocyanidins, was derived from cranberry juice. Human gingival epithelial cells and normal human gingival fibroblasts were incubated with NDM (5-50 μg/mL), IL-17 (0.5-100 ng/mL), or NDM + IL-17 in serum-free medium for 6 d. IL-6 and IL-8 in culture supernatants were measured by ELISA. Membrane damage and viability were assessed by lactate dehydrogenase activity released into cell supernatants and activity of a mitochondrial enzyme, respectively. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons.
  
  
  RESULTS
  In both cell lines, IL-17 (≥ ~5-10 ng/mL) significantly stimulated production of IL-6 (p < 0.005) and IL-8 (p < 0.03). Non-toxic levels of NDM inhibited constitutive IL-6 and IL-8 production by epithelial cells (p ≤ 0.01) and fibroblasts (p ≤ 0.03) as well as IL-17-stimulated cytokine production by epithelial cells [IL-6 (maximum ~80% inhibition; p ≤ 0.0001); IL-8 (maximum ~70% inhibition; p ≤ 0.03)] and fibroblasts [IL-6 (maximum ~90% inhibition; p ≤ 0.0001); IL-8 (maximum ~80% inhibition; p ≤ 0.008)].
  
  
  CONCLUSIONS
  Cranberry NDM inhibition of constitutive and IL-17-stimulated IL-6 and IL-8 production by gingival fibroblasts and epithelial cells suggests that cranberry components could be useful as a host modulatory therapeutic agent to prevent or treat periodontitis.
authors: College of Dentistry, The University of Tennessee Health Science Center, Memphis, TN, USA; Department of Bioscience Research, The University of Tennessee Health Science Center, Memphis, TN, USA.
authors: D A
authors: DA
authors: Tipton
authors: S
authors: S
authors: Cho
authors: N
authors: N
authors: Zacharia
authors: M K
authors: MK
authors: Dabbous
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D018929:Cell Culture Techniques; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004847:Epithelial Cells / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000032:analysis*; D016209:Interleukin-8 / Q000032:analysis* / Q000037:antagonists & inhibitors; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D044945:Proanthocyanidins / Q000494:pharmacology*; D013997:Time Factors; D029799:Vaccinium macrocarpon; D000093242:Interleukin-6 Inhibitors
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D016895:Culture Media, Serum-Free; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D007770:L-Lactate Dehydrogenase; D044945:Proanthocyanidins; D000093242:Interleukin-6 Inhibitors; C508606:CXCL8 protein, human; C508600:IL6 protein, human
keywords: IL-17; cranberry; cytokine; epithelial cell; fibroblast