Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers
Interferon-γ increases expression of the di/tri-peptide transporter, h-PEPT1, and dipeptide transport in cultured human intestinal monolayers
复制标题
DOI：
10.1016/j.phrs.2008.11.001
复制
发表时间：
2009-03-01
影响因子：
9.3
通讯作者：
Welage, Lynda S.
中科院分区：
文献类型：
--
作者：
Foster, David R.;Landowski, Christopher P.;Welage, Lynda S.
二/三肽转运体h-PEPT1在二/三肽和多种药物的口服吸收中起着重要作用。炎症条件可能会影响肠道异种转运蛋白的功能：然而，炎症对h-PEPT1的影响还没有得到很好的描述。本研究旨在探讨炎性细胞因子干扰素-γ对h-PEPT1介导的二肽吸收的影响。在可渗透的载体上生长了CaCO-2单层。测定甘氨酸肌氨酸(Gly-Sar)与干扰素-γ或对照组孵育后的有效根尖-基底侧方通透性(P-Eff)。在4℃和Gly-Sar浓度不断增加的情况下，进行了额外的实验。半定量RT-PCR法检测H-PEPT1的表达。与对照组相比，50 ng/ml的干扰素-γ可使Gly-Sar P-Eff28.61升高(p=0.03)。在4℃下进行的实验中，Gly-Sar P-Eff在干扰素-γ处理的细胞(p=0.003)和HAT中下降了39.6%。在对照中(p=0.006)。在对照组和干扰素-γ处理的细胞中，随着Gly-Sar浓度的升高，细胞的转运呈浓度依赖性。与对照组相比，干扰素-γ50和100 ng/mlh-PEPT1mRNA表达分别增加14.2%和11.5%(p=0.019)。综上所述，干扰素-γ可增加h-PEPT1的表达和二肽Gly-Sar在Caco-2单层中的渗透。这些发现表明，在某些炎症条件下，多肽和模拟多肽药物的肠道吸收可能会增加。(C)2008爱思唯尔有限公司。保留所有权利。
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 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 28.61, compared to controls (p=0.03). in experiments conducted at 4 C, Gly-Sar P-eff decreased 39.6% in IFN-gamma treated cells (p=0.003) and HAT. 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. (C) 2008 Elsevier Ltd. All rights reserved.