Protective effects of vitamin D against injury in intestinal epithelium

Pediatr Surg Int. 2019 Dec;35(12):1395-1401. doi: 10.1007/s00383-019-04586-y. Epub 2019 Oct 14.

Abstract

Background: Vitamin D deficiency is associated with intestinal barrier dysfunction, which contributes to pathogenesis of acute intestinal injury in children. We aim to investigate the effects of vitamin D on intestinal injury in intestinal epithelial cells and organoids.

Methods: Lipopolysaccharide (LPS) was used to induce injury in intestinal epithelial cells (IEC-18) and organoids, and the effect of vitamin D was assessed. Cell viability was measured and inflammation cytokines TNFα and IL-8 were quantified. FITC-dextran 4 kDa (FD4) permeability was measured using Transwell while tight junction markers were assessed by immunofluorescence staining in IEC-18 and intestinal organoids. Data were compared using one-way ANOVA with Bonferroni post-test.

Results: IEC-18 viability was decreased by LPS treatment, but was prevented by vitamin D. The upregulation of inflammation was inhibited by vitamin D, which also decreased epithelium permeability. Vitamin D restored tight junction ZO-1 and claudin 2. In addition, vitamin D decreased TNFα expression and prevented the disruption of ZO-1 in injured organoids.

Conclusions: Vitamin D rescued epithelial barrier function by improving permeability and restoring tight junctions, leading to decrease inflammation. This study confirms the protective effects of vitamin D, which could be used as a treatment strategy for infants at risk of developing intestinal injury.

Keywords: Intestinal epithelial cells; Organoids; Permeability; Vitamin D.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Lipopolysaccharides / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Permeability / drug effects
  • Rats
  • Tight Junctions / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects
  • Vitamin D / pharmacology*
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / drug therapy*
  • Vitamins / pharmacology*

Substances

  • Cytokines
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Vitamins
  • Vitamin D