Effects of cranberry components on IL-1β-stimulated production of IL-6, IL-8 and VEGF by human TMJ synovial fibroblasts

Arch Oral Biol. 2016 Aug:68:88-96. doi: 10.1016/j.archoralbio.2016.04.005. Epub 2016 Apr 22.

Abstract

Objective: Osteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1β (IL-1β) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1β-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells.

Design: Cranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1β (0.001-1nM)±NDM (25-250μg/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-κB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides.

Data analysis: ANOVA and Scheffe's F procedure for post hoc comparisons.

Results: NDM did not affect cell viability but inhibited IL-1β stimulated IL-6, IL-8, and VEGF production in all cell lines (p<0.05). NDM partially reduced nuclear levels of NF-κB and AP-1 (p<0.04), depending upon cell line and time of exposure to IL-1β+NDM.

Conclusion: Cranberry NDM inhibition of IL-1β-stimulated IL- 6, IL-8, and VEGF production by TMJ synovial fibroblast-like cells suggests that cranberry components may be useful as a host modulatory therapeutic agent to prevent or treat inflammatory arthropathies of the TMJ.

Keywords: Cranberry; Cytokine; IL-1β; Synovial fibroblast; TMJ.

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / pharmacology*
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / biosynthesis*
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / biosynthesis*
  • Plant Extracts / pharmacology*
  • Polyphenols / pharmacology
  • Synovial Membrane / cytology
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • Temporomandibular Joint / cytology
  • Temporomandibular Joint / drug effects*
  • Temporomandibular Joint / metabolism
  • Vaccinium macrocarpon / chemistry*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • CXCL8 protein, human
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Plant Extracts
  • Polyphenols
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A