Activation of muscarinic cholinoceptor ameliorates tumor necrosis factor-α-induced barrier dysfunction in intestinal epithelial cells

FEBS Lett. 2015 Nov 30;589(23):3640-7. doi: 10.1016/j.febslet.2015.10.029. Epub 2015 Oct 28.

Abstract

Impaired intestinal barrier function is one of the critical issues in inflammatory bowel diseases. The aim of this study is to investigate muscarinic cholinoceptor (mAChR)-mediated signaling for the amelioration of cytokine-induced barrier dysfunction in intestinal epithelium. Rat colon challenged with TNF-α and interferon γ reduced transepithelial electrical resistance (TER). This barrier injury was attenuated by muscarinic stimulation. In HT-29/B6 intestinal epithelial cells, muscarinic stimulation suppressed TNF-α-induced activation of NF-κB signaling and barrier disruption. Finally, muscarinic stimulation promoted the shedding of TNFR1, which would be a mechanism for the attenuation of TNF-α/NF-κB signaling and barrier disruption via mAChR.

Keywords: Inflammatory bowel disease (IBD); Intestinal barrier; Intestinal epithelium; Muscarinic acetylcholine receptor; Tumor necrosis factor (TNF).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colon / cytology
  • HT29 Cells
  • Humans
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • NF-kappa B / metabolism
  • Rats
  • Receptors, Muscarinic / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • NF-kappa B
  • Receptors, Muscarinic
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha