- 作者：Jennifer Kovacs-Nolan ; Hua Zhang ; Masahisa Ibuki ; Toshihiro Nakamori ; Keiko Yoshiura ; Patricia V. Turner ; Toshiro Matsui ; Yoshinori Mine
- 关键词：Soy peptide ; PepT1 ; Inflammatory bowel disease (IBD) ; Anti-inflammatory ; Dextran sodium sulfate (DSS) ; Pro-inflammatory cytokine
- 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
- 出版年：2012
- 出版时间：November, 2012
- 年：2012
- 卷：1820
- 期：11
- 页码：1753-1763
- 全文大小：1450 K
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-¦Á, 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-¦Á, IL-6, IL-1¦Â, IFN-¦Ã 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.