The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation

Jennifer Kovacs-Nolan, Hua Zhang, Masahisa Ibuki, Toshihiro Nakamori, Keiko Yoshiura, Patricia V. Turner, Toshiro Matsui, Yoshinori Mine

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1753-1763
Number of pages11
JournalBiochimica et Biophysica Acta - General Subjects
Volume1820
Issue number11
DOIs
Publication statusPublished - Nov 1 2012

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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