Cholecalciterol cholesterol emulsion ameliorates experimental colitis via down-regulating the pyroptosis signaling pathway

Exp Mol Pathol. 2016 Jun;100(3):386-92. doi: 10.1016/j.yexmp.2016.03.003. Epub 2016 Mar 9.

Abstract

The therapeutic effect of 1,25(OH)2 vitamin D3 and its analog (paricalcitol) on experimental colitis in animals has been heavily demonstrated. However, the response to Cholecalciterol Cholesterol Emulsion (CCE), a precursor of 1,25(OH)2 vitamin D3, has not yet been reported. Whether pyroptosis is involved in colitic deterioration also remains unclear. Therefore, we adopted molecular biology and histology approaches to examine mechanisms by which CCE was able to regulate experimental colitis in the animal model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Our data revealed that mice displayed a remarkable reduction in colonic histological scores, colonic inflammation and colonic histological damage. In addition, there was an overall improvement in general status (change in body weight, food and water intake, mental status, activity) and a 30% increase in survival rate due to the downregulation of pyroptosis following treatment with CCE. In conclusion, our data have provided evidence that CCE can attenuate the damage of experimental colitis by suppressing pyroptosis signaling.

Keywords: CCE; IBD; Pyroptosis; TNBS; VDR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Calcitriol / chemistry
  • Calcitriol / pharmacology*
  • Calcitriol / therapeutic use
  • Calcium / blood
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Child
  • Child, Preschool
  • Cholecalciferol / chemistry
  • Cholecalciferol / pharmacology*
  • Cholecalciferol / therapeutic use
  • Cholesterol / chemistry
  • Cholesterol / pharmacology*
  • Cholesterol / therapeutic use
  • Colitis / chemically induced
  • Colitis / mortality
  • Colitis / prevention & control*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Emulsions
  • Female
  • Gene Expression / drug effects
  • Humans
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Mice, Inbred BALB C
  • Phosphorus / blood
  • Pyroptosis / drug effects*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Survival Rate
  • Trinitrobenzenesulfonic Acid
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy
  • Vitamins / chemistry
  • Vitamins / pharmacology
  • Vitamins / therapeutic use

Substances

  • Emulsions
  • Interleukin-18
  • Interleukin-1beta
  • Vitamins
  • Cholecalciferol
  • Phosphorus
  • Trinitrobenzenesulfonic Acid
  • Cholesterol
  • Caspase 1
  • Calcitriol
  • Calcium