KPV
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 KPV anti-inflammatory effect is PepT1-mediated in intestinal epithelial and immune cells, and 2) examine KPV anti-inflammatory effect in two models of mice colitis.
Methods
Human intestinal epithelial cells (Caco2-BBE and HT29-Cl.19A), and human T cells (Jurkat) were stimulated with pro-inflammatory cytokines in the presence or absence of KPV. KPV anti-inflammatory effect was assessed using a NF-κB luciferase gene reporter, western blot, real-time RT-PCR and ELISA. Uptake experiments were performed using cold KPV as a competitor for hPepT1 radiolabelled substrate or using [3H]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 histological level and by pro-inflammatory cytokine mRNA expression.
Results
Nanomolar concentrations of KPV inhibit the activation of NF-κB and MAP kinase inflammatory signaling pathways, and reduce pro-inflammatory cytokine secretion. We found that KPV acts via hPepT1 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.
Conclusion
This study indicates that KPV is transported into cells by PepT1 and might be a new therapeutic agent for IBD.
INTRODUCTION
One of the normal transport functions of gut epithelial cells is the absorption of small peptides from the diet by peptide transport activity (1). This is mediated via the H+-coupled oligopeptide transporter (PepT1) which is located at the apical membrane of intestinal epithelial cells (IEC) and which cotransports peptides and H+ (2). The specificity of hPepT1 is broad and includes many di- and tripeptides in addition to various peptide-derived drugs (3–8). PepT1 is mainly expressed in brush-border membranes of enterocytes in the small intestine, in proximal tubular cells of the S1 segment of the kidney, and in bile-duct epithelial cells (4, 5, 9–15). By contrast, in the colon, expression of PepT1 mRNA and protein is low (16) and sometimes cannot be detected (10, 15, 17). Although human PepT1 is not expressed in normal colonic epithelial cells (10, 16, 17), we detected its expression at the apical membrane of epithelial cells in chronically inflamed colon (17). Interestingly, we have also shown that immune cells, such as macrophages, which are in close contact with the lamina propria of the intestine, also express PepT1 at their membranes
Be the first to review “KPV”
Related products
PEPTIDES
PEPTIDES
PEPTIDES
PEPTIDES
PEPTIDES
PEPTIDES
PEPTIDES
PEPTIDES
Reviews
There are no reviews yet.