Interferon-gamma increases hPepT1-mediated uptake of di-tripeptides including the bacterial tripeptide fMLP in polarized intestinal epithelia.
Interferon-gamma causes a global phenotypic switch in intestinal epithelial function, in which enterocytes become immune accessory cells. The phenotypic switch is characterized by a down-regulation of membrane transporters and up-regulation of immune accessory molecules in intestinal epithelial cells. However, the effect of interferon-gamma on the intestinal epithelia di-tripeptide hPepT1 transporter has not been investigated. In this study we demonstrate that 1) interferon-gamma increases di-tripeptide uptake in dose- and time-dependent manner in model intestinal epithelia (Caco-2 BBE cell monolayers), 2) the increase in di-tripeptides induced by interferon-gamma is hPepT1 mediated, 3) interferon-gamma does not affect the hPept1 expression at the mRNA and protein levels 4) interferon-gamma increases the intracellular pH and consequently enhances the H+-electrochemical gradient across apical plasma membrane in model intestinal epithelia (Caco2-BBE monolayers). We suggest that interferon-gamma could increase the hPepT1 mediated di-tripeptides uptake in inflamed epithelial cells. Under these conditions, interferon-gamma will increase the intracellular amount of such diverse prokaryotic and eucaryotic small di-tripeptides in inflamed epithelial cells. The intracellular accumulation of such di-tripeptides may be important in enterocytes becoming immune accessory cells.
Department of Medicine, Division of Digestive Diseases, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA.
Marion
M
Buyse
Laetitia
L
Charrier
Shanthi
S
Sitaraman
Andrew
A
Gewirtz
Didier
D
Merlin
D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D016764:Cell Polarity / Q000187:drug effects; D003593:Cytoplasm / Q000737:chemistry / Q000187:drug effects; D004151:Dipeptides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D000074011:Peptide Transporter 1; D027981:Symporters; D013997:Time Factors
D000998:Antiviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004151:Dipeptides; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; D027981:Symporters; D007371:Interferon-gamma