gamma-Glutamyl cysteine and gamma-glutamyl valine inhibit TNF-alpha signaling in intestinal epithelial cells and reduce inflammation in a mouse model of colitis via allosteric activation of the calcium-sensing receptor

摘要

Background: The extracellular calcium-sensing receptor (CaSR) is distributed throughout the gastrointestinal tract, and its activation has been shown to promote intestinal homeostasis, suggesting that CaSR may be a promising target for novel therapies to prevent chronic intestinal inflammation such as inflammatory bowel disease (IBD). The gamma-glutamyl dipeptides gamma-glutamyl cysteine (gamma-EC) and gamma-glutamyl valine (gamma-EV) are dietary flavor enhancing compounds, and have been shown to activate CaSR via allosteric ligand binding. The aim of this study was to examine the anti-inflammatory effects of gamma-EC and gamma-EV in vitro in intestinal epithelial cells and in a mouse model of intestinal inflammation.