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PepT1‐mediated anti‐inflammatory tri‐peptide (KPV) transport reduces intestinal inflammation
Author(s) -
Dalmasso Guillaume,
Garg Pallavi,
Sitaraman Shanthi V,
Merlin Didier
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a586-c
Subject(s) - intracellular , inflammation , chemistry , secretion , biochemistry , p38 mitogen activated protein kinases , microbiology and biotechnology , kinase , biology , protein kinase a , immunology
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.