| First Author | Kovacs-Nolan J | Year | 2012 |
| Journal | Biochim Biophys Acta | Volume | 1820 |
| Issue | 11 | Pages | 1753-63 |
| PubMed ID | 22842481 | Mgi Jnum | J:188035 |
| Mgi Id | MGI:5439036 | Doi | 10.1016/j.bbagen.2012.07.007 |
| Citation | Kovacs-Nolan J, et al. (2012) The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation. Biochim Biophys Acta 1820(11):1753-63 |
| abstractText | 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-alpha, 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-alpha, IL-6, IL-1beta, IFN-gamma 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. |
