The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation.
Kovacs-Nolan J, Zhang H, Ibuki M, Nakamori T, Yoshiura K, Turner PV, Matsui T, Mine Y., Biochim Biophys Acta., 2012, 1820, 1753-63. Epub 2012 Jul 27. DOI: 10.1016/j.bbagen.2012.07.007
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.
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.
VPY inhibited the secretion of IL-8 and TNF-Î±, 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-Î±, IL-6, IL-1Î², IFN-Î³ 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.
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