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-γ (IFN-γ) on h-PEPT1 mediated dipeptide absorption. Caco-2 monolayers were grown on permeable supports. The effective apical-to-basolateral permeability (Peff) of glycylsarcosine (Gly-Sar) was measured following incubation with IFN-γ 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-γ 50 ng/ml increased Gly-Sar Peff 28.6% compared to controls (p = 0.03). In experiments conducted at 4 °C, Gly-Sar Peff decreased 39.6% in IFN-γ treated cells (p = 0.003) and 28.4% in controls (p = 0.006). In controls and IFN-γ treated cells, concentration dependent transport was seen with escalating concentrations of Gly-Sar. Compared to controls, IFN-γ 50 and 100 ng/ml increased h-PEPT1 mRNA expression by 14.2% and 11.5%, respectively (p = 0.019). In summary, IFN-γ 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.
- Caco-2 cells