Quercetin Exposure Suppresses the Inflammatory Pathway in Intestinal Organoids from Winnie Mice

Int J Mol Sci. 2019 Nov 16;20(22):5771. doi: 10.3390/ijms20225771.

Abstract

Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine model Winnie to explore if the chronic inflammatory features observed in the parental intestine were preserved by the organoids. Furthermore, we investigated if quercetin administration to in vitro cultured organoids could suppress LPS-induced inflammation in wild-type organoids (WT-organoids) and spontaneous inflammation in ulcerative colitis organoids (UC-organoids). Our data demonstrate that small intestinal organoids obtained from Winnie mice retain the chronic intestinal inflammatory features characteristic of the parental tissue. Quercetin administration was able to suppress inflammation both in UC-organoids and in LPS-treated WT-organoids. Altogether, our data demonstrate that UC-organoids are a reliable experimental system for investigating chronic intestinal inflammation and pharmacological responses.

Keywords: inflammatory bowel diseases; quercetin; small intestinal organoids.

MeSH terms

  • Animals
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / pathology
  • Disease Models, Animal
  • Gene Expression / drug effects
  • In Vitro Techniques
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / ultrastructure
  • Lipocalin-2 / genetics
  • Lipocalin-2 / metabolism
  • Lipopolysaccharides / toxicity
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Quercetin / pharmacology*
  • Secretory Leukocyte Peptidase Inhibitor / genetics
  • Secretory Leukocyte Peptidase Inhibitor / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Lipocalin-2
  • Lipopolysaccharides
  • Secretory Leukocyte Peptidase Inhibitor
  • Slpi protein, mouse
  • Tumor Necrosis Factor-alpha
  • Lcn2 protein, mouse
  • Quercetin