Expression and regulation of proton-coupled oligopeptide transporters in colonic tissue and immune cells of mice

Abstract

A number of studies have implicated proton-coupled oligopeptide transporters (POTs) in the initiation and/or progression of inflammatory bowel disease and immune cell signaling. With this in mind, the aim of this study was to delineate the expression of POTs in mouse colonic tissues and immune cells, and characterize the potential role of these transporters in nucleotide-binding oligomerization domain (NOD) signaling. Using a dextran sodium sulfate (DSS)-induced colitis mouse model, we found that DSS down regulated Pht1 gene expression and up regulated Pht2 gene expression in colonic tissue and immune cells. In contrast, PEPT1 protein was absent from the colonic tissue and immune cells of normal and DSS-treated mice. NOD ligands, muramyl dipeptide (MDP) and l-Ala-γ-d-Glu-meso-diaminopimelic acid (tri-DAP), were shown to be substrates of PHT2 in MDCK-hPHT2 cells. Subsequent studies revealed that the immune response of lamina propia mononuclear cells may be regulated by PHT1 and PHT2, and that PHT2 facilitated the NOD-dependent immune response in RAW264.7 macrophages. These results clarified the expression of POTs in mouse colonic segments, cells and subtypes, and the role of increased Pht2 expression during chemically-induced colitis in facilitating NOD-dependent immune response. The findings further suggest that intestinal PHT2 may serve as a therapeutic target for IBD therapy.

The Radiolabeling of a Gly-Sar Dipeptide Derivative with Flourine-18 and Its Use as a Potential Peptide Transporter PET Imaging Agent

“…B C Furthermore, we found similar [ 18 F]FEPPG 1 uptake on PET imaging 30 min after injection of 3.7-5.5 MBq (100-150 µCi) of [ 18 F]FEPPG 1 (Figure 3B,C) in subcutaneous xenograft models of all pancreatic cancer cell lines tested (Panc1, BxPC3, and AsPC1). As expected, higher amounts of [ 18 F]FEPPG 1 uptake were observed in the liver and kidneys, in line with the transporter expression and excretion [21][22][23] (Figure 3B and data not shown).…”

Regulation and biological role of the peptide/histidine transporter SLC15A3 in Toll-like receptor-mediated inflammatory responses in macrophage

“…Macrophages play a crucial role in pathogen recognition and the clearance of bacteria and bacterial components, as they are equipped with a wide range of pattern recognition receptors 16 . Since Slc15a3 is highly expressed in macrophages and responsible for transporting some bacterial components across biological membranes 17 , we investigated whether Slc15a3 could be regulated by TLR4 activation. As shown in Fig.…”

SLC15A2 and SLC15A4 Mediate the Transport of Bacterially Derived Di/Tripeptides To Enhance the Nucleotide-Binding Oligomerization Domain–Dependent Immune Response in Mouse Bone Marrow–Derived Macrophages

“…Thus, it is uncertain as to whether or not PEPT1 protein would be found in the colon of native tissue, especially in colonic immune cells. Recently, we reported that PEPT1 protein was absent from the colonic tissue and immune cells of normal mice and DSS-treated mice (26). Our current study confirms this finding in that neither PEPT1 transcripts nor protein were observed in mouse bone marrow (Fig.…”