Study summary · research use only
PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this study using human cell lines and mouse colitis models, the authors examined the tripeptide KPV (Lys-Pro-Val) and the transporter PepT1. Human intestinal epithelial cells (Caco2-BBE, HT29-Cl.19A) and human T cells (Jurkat) were stimulated with pro-inflammatory cytokines with or without KPV, assessed with an NF-kappaB luciferase reporter, Western blot, RT-PCR, and ELISA. Uptake experiments used cold KPV as competitor and [3H]KPV for kinetics. The abstract reports that nanomolar KPV inhibited NF-kappaB and MAP kinase signaling and reduced pro-inflammatory cytokine secretion, acting via PepT1 expressed in immune and epithelial cells. In DSS- and TNBS-induced colitis in mice, oral KPV reduced the incidence of colitis with decreased pro-inflammatory cytokine expression. The authors conclude KPV is transported by PepT1 and might be a therapeutic agent for inflammatory bowel disease.
Abstract
KPV is a tripeptide (Lys-Pro-Val), which possesses anti-inflammatory properties; however, its mechanisms of action still remain unknown. PepT1 is a di/tripeptide transporter normally expressed in the small intestine and induced in colon during inflammatory bowel disease (IBD). The aim of this study was to 1) investigate whether the KPV anti-inflammatory effect is PepT1-mediated in intestinal epithelian and immune cells, and 2) examine the anti-inflammatory effects in two models of mice colitis. Human intestinal epithelial cells Caco2-BBE, HT29-Cl.19A, and human T cells (Jurkat) were stimulated with pro-inflammatory cytokines in the present or absence of KPV. KPV anti-inflammatory effect was assessed using a NF-kappaB luciferase gene reporter, Western blot, real-time RT-PCR and ELISA. Uptake experiments were performed using cold KPV as a competitor for PepT1 radiolabelled substrate or using [(3)H]KPV to determine kinetic characteristics of KPV uptake. Anti-inflammatory effect of KPV was also investigated in DSS- and TNBS-induced colitis in mice. KPV was added to drinking water and inflammation was assessed at the histologic level and by proinflammatory cytokine mRNA expression. Nanomolar concentrations of KPV inhibit the activation of NF-kappaB and MAP kinase inflammatory signaling pathways, and reduce pro-inflammatory cytokine secretion. We found that KPV acts via PepT1 expressed in immune and intestinal epithelial cells. Furthermore, oral administration of KPV reduces the incidence of DSS- and TNBS-induced colitis indicated by a decrease in pro-inflammatory cytokine expression. This study indicates tht KPV is transported into cells by PepT1 and might be a new therapeutic agent for IBD.
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