Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers

David R. Foster, Christopher P. Landowski, Xiaomei Zheng, Gordon L. Amidon, Lynda S. Welage (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

12 Citations (Scopus)

Abstract

The di/tri-peptide transporter h-PEPT1 plays an important role in the oral absorption of di/tri-peptides and numerous drugs. Inflammatory conditions may influence intestinal xenobiotic transporter function; however, the effects of inflammation on h-PEPT1 have not been well described. This study was conducted to determine the effects of the inflammatory cytokine interferon-gamma (IFN-gamma) on h-PEPT1 mediated dipeptide absorption. Caco-2 monolayers were grown on permeable supports. The effective apical-to-basolateral permeability (P(eff)) of glycylsarcosine (Gly-Sar) was measured following incubation with IFN-gamma or control media. Additional experiments were conducted at 4 degrees C, and with escalating concentrations of Gly-Sar. h-PEPT1 expression was determined using semiquantitative RT-PCR. IFN-gamma 50 ng/ml increased Gly-Sar P(eff) 28.6% compared to controls (p=0.03). In experiments conducted at 4 degrees C, Gly-Sar P(eff) decreased 39.6% in IFN-gamma treated cells (p=0.003) and 28.4% in controls (p=0.006). In controls and IFN-gamma treated cells, concentration dependent transport was seen with escalating concentrations of Gly-Sar. Compared to controls, IFN-gamma 50 and 100 ng/ml increased h-PEPT1 mRNA expression by 14.2% and 11.5%, respectively (p=0.019). In summary, IFN-gamma increases h-PEPT1 expression and permeation of the dipeptide Gly-Sar in Caco-2 monolayers. These findings imply that intestinal absorption of peptides and peptidomimetic drugs may be increased in certain inflammatory conditions.
Original languageEnglish
Pages (from-to)215-20
JournalPharmacological Research
Volume59
Issue number3
DOIs
Publication statusPublished - Mar 2009
MoE publication typeNot Eligible

Fingerprint

Dipeptides
Interferons
Interferon-gamma
Peptidomimetics
Peptides
Intestinal Absorption
Xenobiotics
peptide permease
Pharmaceutical Preparations
glycylsarcosine
Permeability
Cytokines
Inflammation
Polymerase Chain Reaction
Messenger RNA

Cite this

Foster, David R. ; Landowski, Christopher P. ; Zheng, Xiaomei ; Amidon, Gordon L. ; Welage, Lynda S. / Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers. In: Pharmacological Research. 2009 ; Vol. 59, No. 3. pp. 215-20.
@article{93af340361ce468e8df94476735e4ff9,
title = "Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers",
abstract = "The di/tri-peptide transporter h-PEPT1 plays an important role in the oral absorption of di/tri-peptides and numerous drugs. Inflammatory conditions may influence intestinal xenobiotic transporter function; however, the effects of inflammation on h-PEPT1 have not been well described. This study was conducted to determine the effects of the inflammatory cytokine interferon-gamma (IFN-gamma) on h-PEPT1 mediated dipeptide absorption. Caco-2 monolayers were grown on permeable supports. The effective apical-to-basolateral permeability (P(eff)) of glycylsarcosine (Gly-Sar) was measured following incubation with IFN-gamma or control media. Additional experiments were conducted at 4 degrees C, and with escalating concentrations of Gly-Sar. h-PEPT1 expression was determined using semiquantitative RT-PCR. IFN-gamma 50 ng/ml increased Gly-Sar P(eff) 28.6{\%} compared to controls (p=0.03). In experiments conducted at 4 degrees C, Gly-Sar P(eff) decreased 39.6{\%} in IFN-gamma treated cells (p=0.003) and 28.4{\%} in controls (p=0.006). In controls and IFN-gamma treated cells, concentration dependent transport was seen with escalating concentrations of Gly-Sar. Compared to controls, IFN-gamma 50 and 100 ng/ml increased h-PEPT1 mRNA expression by 14.2{\%} and 11.5{\%}, respectively (p=0.019). In summary, IFN-gamma increases h-PEPT1 expression and permeation of the dipeptide Gly-Sar in Caco-2 monolayers. These findings imply that intestinal absorption of peptides and peptidomimetic drugs may be increased in certain inflammatory conditions.",
author = "Foster, {David R.} and Landowski, {Christopher P.} and Xiaomei Zheng and Amidon, {Gordon L.} and Welage, {Lynda S.}",
year = "2009",
month = "3",
doi = "10.1016/j.phrs.2008.11.001",
language = "English",
volume = "59",
pages = "215--20",
journal = "Pharmacological Research",
issn = "1043-6618",
publisher = "Academic Press",
number = "3",

}

Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers. / Foster, David R.; Landowski, Christopher P. ; Zheng, Xiaomei; Amidon, Gordon L. ; Welage, Lynda S. (Corresponding Author).

In: Pharmacological Research, Vol. 59, No. 3, 03.2009, p. 215-20.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers

AU - Foster, David R.

AU - Landowski, Christopher P.

AU - Zheng, Xiaomei

AU - Amidon, Gordon L.

AU - Welage, Lynda S.

PY - 2009/3

Y1 - 2009/3

N2 - The di/tri-peptide transporter h-PEPT1 plays an important role in the oral absorption of di/tri-peptides and numerous drugs. Inflammatory conditions may influence intestinal xenobiotic transporter function; however, the effects of inflammation on h-PEPT1 have not been well described. This study was conducted to determine the effects of the inflammatory cytokine interferon-gamma (IFN-gamma) on h-PEPT1 mediated dipeptide absorption. Caco-2 monolayers were grown on permeable supports. The effective apical-to-basolateral permeability (P(eff)) of glycylsarcosine (Gly-Sar) was measured following incubation with IFN-gamma or control media. Additional experiments were conducted at 4 degrees C, and with escalating concentrations of Gly-Sar. h-PEPT1 expression was determined using semiquantitative RT-PCR. IFN-gamma 50 ng/ml increased Gly-Sar P(eff) 28.6% compared to controls (p=0.03). In experiments conducted at 4 degrees C, Gly-Sar P(eff) decreased 39.6% in IFN-gamma treated cells (p=0.003) and 28.4% in controls (p=0.006). In controls and IFN-gamma treated cells, concentration dependent transport was seen with escalating concentrations of Gly-Sar. Compared to controls, IFN-gamma 50 and 100 ng/ml increased h-PEPT1 mRNA expression by 14.2% and 11.5%, respectively (p=0.019). In summary, IFN-gamma increases h-PEPT1 expression and permeation of the dipeptide Gly-Sar in Caco-2 monolayers. These findings imply that intestinal absorption of peptides and peptidomimetic drugs may be increased in certain inflammatory conditions.

AB - The di/tri-peptide transporter h-PEPT1 plays an important role in the oral absorption of di/tri-peptides and numerous drugs. Inflammatory conditions may influence intestinal xenobiotic transporter function; however, the effects of inflammation on h-PEPT1 have not been well described. This study was conducted to determine the effects of the inflammatory cytokine interferon-gamma (IFN-gamma) on h-PEPT1 mediated dipeptide absorption. Caco-2 monolayers were grown on permeable supports. The effective apical-to-basolateral permeability (P(eff)) of glycylsarcosine (Gly-Sar) was measured following incubation with IFN-gamma or control media. Additional experiments were conducted at 4 degrees C, and with escalating concentrations of Gly-Sar. h-PEPT1 expression was determined using semiquantitative RT-PCR. IFN-gamma 50 ng/ml increased Gly-Sar P(eff) 28.6% compared to controls (p=0.03). In experiments conducted at 4 degrees C, Gly-Sar P(eff) decreased 39.6% in IFN-gamma treated cells (p=0.003) and 28.4% in controls (p=0.006). In controls and IFN-gamma treated cells, concentration dependent transport was seen with escalating concentrations of Gly-Sar. Compared to controls, IFN-gamma 50 and 100 ng/ml increased h-PEPT1 mRNA expression by 14.2% and 11.5%, respectively (p=0.019). In summary, IFN-gamma increases h-PEPT1 expression and permeation of the dipeptide Gly-Sar in Caco-2 monolayers. These findings imply that intestinal absorption of peptides and peptidomimetic drugs may be increased in certain inflammatory conditions.

U2 - 10.1016/j.phrs.2008.11.001

DO - 10.1016/j.phrs.2008.11.001

M3 - Article

VL - 59

SP - 215

EP - 220

JO - Pharmacological Research

JF - Pharmacological Research

SN - 1043-6618

IS - 3

ER -