RRC ID 43981
Author Kovacs-Nolan J, Zhang H, Ibuki M, Nakamori T, Yoshiura K, Turner PV, Matsui T, Mine Y.
Title The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation.
Journal Biochim Biophys Acta
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 AND GENERAL SIGNIFICANCE: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.
Volume 1820(11)
Pages 1753-63
Published 2012-11-1
DOI 10.1016/j.bbagen.2012.07.007
PII S0304-4165(12)00212-7
PMID 22842481
MeSH Animals Anti-Inflammatory Agents / pharmacology* Caco-2 Cells Colitis / drug therapy* Colitis / immunology Cytokines / antagonists & inhibitors Cytokines / genetics Humans Interleukin-6 / genetics Mice Oligopeptides / pharmacology* Peptide Transporter 1 Peroxidase / metabolism Soybean Proteins / pharmacology* Symporters / metabolism* Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / metabolism
IF 3.411
Times Cited 72
Human and Animal Cells THP-1(RCB1189)