PepT1‐mediated anti‐inflammatory tri‐peptide (KPV) transport reduces intestinal inflammation

Abstract

Since we previously demonstrated that hPepT1 is expressed in inflamed colonic epithelial cells, we hypothesized that colonic-expressed hPepT1 could be used for uptake of small anti-inflammatory peptides. Here, we demonstrate that the anti-inflammatory peptide, KPV (Lys-Pro-Val), inhibits hPepT1-mediated [14C] Glycine-Sarcosine uptake by 50% in Caco2-BBE monolayers, and addition of KPV to the apical plasma membranes of Caco2-BBE monolayers induces rapid intracellular acidification. Furthermore, Caco2-BBE cells incubated with KPV prior to Il-1beta treatment show reduced activation of NF-kB and MAP kinases (ERK1/2, JNK, p38) and decreased secretion of IL-8. Finally, we found that oral administration of KPV reduces DSS-induced intestinal inflammation in mice. These data collectively suggest that colonic-expressed PepT1 may transport tri-peptides (e.g. KPV), leading to decreased activation of intracellular inflammatory signaling pathways.