Mangiferin inhibits lipopolysaccharide-induced production of interleukin-6 in human oral epithelial cells by suppressing toll-like receptor signaling

Arch Oral Biol. 2016 Nov:71:155-161. doi: 10.1016/j.archoralbio.2016.08.003. Epub 2016 Aug 4.

Abstract

Objective: Oral epithelial cells have currently been found to play an important role in inflammatory modulation in periodontitis. Mangiferin is a natural glucosylxanthone with anti-inflammatory activity. The aim of this study was to investigate the regulatory effect of mangiferin on lipopolysaccharide (LPS)-induced production of proinflammatory cytokine interleukin-6 (IL-6) in oral epithelial cells and the underlying mechanisms.

Design: The levels of LPS-induced IL-6 production in OKF6/TERT-2 oral keratinocytes were detected using enzyme-linked immunosorbent assay (ELISA). The expression of Toll-like receptor (TLR) 2 and TLR4 was determined using western blot analysis. And the phosphorylation of TLR downstream nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) was examined using cell-based protein phosphorylation ELISA kits.

Results: We found that mangiferin reduced LPS-upregulated IL-6 production in OKF6/TERT-2 cells. Additionally, mangiferin inhibited LPS-induced TLR2 and TLR4 overexpression, and suppressed the phosphorylation of NF-κB, p38 MAPK and JNK. Moreover, mangiferin repressed IL-6 production and TLR signaling activation in a dose-dependent manner after 24h treatment.

Conclusions: Mangiferin decreases LPS-induced production of IL-6 in human oral epithelial cells by suppressing TLR signaling, and this glucosylxanthone may have potential for the treatment of periodontitis.

Keywords: Interleukin-6; Lipopolysaccharide; Mangiferin; Oral epithelial cells; Toll-like receptors.

MeSH terms

  • Blotting, Western
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-6 / metabolism*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism*
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / metabolism
  • Phosphorylation
  • Signal Transduction / drug effects
  • Toll-Like Receptors / drug effects
  • Xanthones / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Toll-Like Receptors
  • Xanthones
  • mangiferin
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases