PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation.

摘要: Background & Aims: KPV is a tripeptide (Lys-Pro-Val), which possesses anti-inflammatory properties; however, its mechanisms of action still remain unknown. PepT1 di/tripeptide transporter normally expressed in the small intestine and induced colon during inflammatory bowel disease (IBD). The aim this study was to 1) investigate whether effect PepT1-mediated intestinal epithelian immune cells, 2) examine effects two models mice colitis. Methods: Human epithelial cells Caco2-BBE, HT29-Cl.19A, human T (Jurkat) were stimulated with pro-inflammatory cytokines present or absence KPV. assessed using NF-κB luciferase gene reporter, Western blot, real-time RT-PCR ELISA. Uptake experiments performed cold as competitor for radiolabelled substrate [3H]KPV determine kinetic characteristics uptake. Anti-inflammatory also investigated DSS- TNBS-induced colitis mice. added drinking water inflammation at histologic level by proinflammatory cytokine mRNA expression. Results: Nanomolar concentrations inhibit activation MAP kinase signaling pathways, reduce secretion. We found that acts via cells. Furthermore, oral administration reduces incidence indicated decrease Conclusions: This indicates tht transported into might be new therapeutic agent IBD.