title: The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation.
abstract: BACKGROUND
  Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract. The peptide transporter PepT1 is responsible for the intestinal uptake of dietary peptides, and its expression in the gastrointestinal tract is up-regulated during intestinal inflammation, indicating that PepT1 may be a promising target for IBD therapeutics.
  
  
  METHODS
  The transport of soy-derived di- and tripeptides across Caco-2 intestinal epithelial cells was examined, and the anti-inflammatory effects of the transported peptide VPY were evaluated in vitro in Caco-2 and THP-1 macrophages, and in vivo in a mouse model of DSS-induced colitis.
  
  
  RESULTS
  VPY inhibited the secretion of IL-8 and TNF-α, respectively, from Caco-2 and THP-1 cells. VPY transport and anti-inflammatory activity in Caco-2 cells was reduced in the presence of Gly-Sar, indicating this activity was mediated by PepT1. In mice, VPY treatment reduced DSS-induced colitis symptoms and weight loss, improved colon histology, reduced MPO activity, and decreased gene expression of the pro-inflammatory cytokines TNF-α, IL-6, IL-1β, IFN-γ and IL-17 in the colon.
  
  
  CONCLUSIONS
  VPY is a novel PepT1 substrate that can inhibit the production of pro-inflammatory mediators in vitro in intestinal epithelial and immune cells, and reduce the severity of colitis in mice by down-regulating the expression of pro-inflammatory cytokines in the colon, suggesting that VPY may be promising for the treatment of IBD.
authors: Department of Food Science, University of Guelph, Guelph, ON, Canada.
authors: Jennifer
authors: J
authors: Kovacs-Nolan
authors: Hua
authors: H
authors: Zhang
authors: Masahisa
authors: M
authors: Ibuki
authors: Toshihiro
authors: T
authors: Nakamori
authors: Keiko
authors: K
authors: Yoshiura
authors: Patricia V
authors: PV
authors: Turner
authors: Toshiro
authors: T
authors: Matsui
authors: Yoshinori
authors: Y
authors: Mine
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018938:Caco-2 Cells; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D000074011:Peptide Transporter 1; D009195:Peroxidase / Q000378:metabolism; D030262:Soybean Proteins / Q000494:pharmacology*; D027981:Symporters / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D015850:Interleukin-6; D009842:Oligopeptides; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; D030262:Soybean Proteins; D027981:Symporters; D014409:Tumor Necrosis Factor-alpha; C576277:VPY tripeptide; D009195:Peroxidase