1,25-dihydroxyvitamin D 3 suppresses lipopolysaccharide-induced interleukin-6 production through aryl hydrocarbon receptor/nuclear factor-κB signaling in oral epithelial cells

BMC Oral Health. 2019 Nov 4;19(1):236. doi: 10.1186/s12903-019-0935-x.

Abstract

Background: Antiinflammatory effect of 1,25-dihydroxyvitamin D3 (1,25D3) has been reported in periodontitis, but the exact mechanisms remain unclear. Oral epithelial cells are recently highlighted as an important regulator of inflammation in this disease. This in vitro study was established to investigate the effect of 1,25D3 on key proinflammatory cytokine IL-6 production and aryl hydrocarbon receptor (AhR)/nuclear factor-κB (NF-κB) signaling in oral epithelial cells upon the stimulation of lipopolysaccharide (LPS) from periodontal pathogens.

Methods: OKF6/TERT-2 oral keratinocytes were incubated with LPS and different concentrations of 1,25D3, and levels of IL-6 production were determined using enzyme-linked immunosorbent assay (ELISA). Expression of vitamin D receptor (VDR), and activation of AhR was examined using western blot analysis, and phosphorylation of NF-κB was detected using cell-based protein phosphorylation ELISA.

Results: 1,25D3 inhibited LPS-induced IL-6 overexpression in OKF6/TERT-2 cells. Additionally, 1,25D3 increased VDR expression and AhR activation, and repressed NF-κB phosphorylation. Furthermore, 1,25D3 suppressed IL-6 expression and enhanced VDR expression and regulated AhR/NF-κB signaling activation in a dose-dependent manner after 48 h treatment.

Conclusions: These results suggest that 1,25D3 may inhibit LPS-induced IL-6 overexpression in human oral epithelial cells through AhR/NF-κB signaling. Our findings may provide an explanation for the antiinflammatory effect and therapeutic benefit of 1,25D3 in periodontitis.

Keywords: 1,25-dihydroxyvitamin D3; Aryl hydrocarbon receptor; Interleukin-6; Nuclear factor-κB; Oral epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cholecalciferol / administration & dosage*
  • Epithelial Cells*
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Lipopolysaccharides / administration & dosage
  • NF-kappa B / drug effects*
  • Receptors, Aryl Hydrocarbon*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology

Substances

  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • Receptors, Aryl Hydrocarbon
  • Vitamin D
  • Cholecalciferol
  • 1,25-dihydroxyvitamin D