Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.150
Effects of the Antidiabetic Drugs Evogliptin and Sitagliptin on the Immune Function of CD26/DPP4 in Th1 Cells
Hyunyee Yoon1,2, Ji Hyun Sung3 and Moon Jung Song1,*
1Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841,
2Protein Immunology Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul 03082,
3Flow Cytometry Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul 03082, Republic of Korea
*E-mail: moonsong@korea.ac.kr
Tel: +82-2-3290-3019, Fax: +82-2-3290-3040
Received: August 30, 2020; Revised: October 7, 2020; Accepted: October 12, 2020; Published online: November 5, 2020.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
This study aimed to investigate whether the antidiabetic drugs dipeptidyl peptidase 4 (DPP4) inhibitors such as evogliptin and sitagliptin affect the membrane DPP4 (mDPP4) enzymatic activity and immune function of T helper1 (Th1) cells in terms of cytokine expression and cell profiles. The mDPP4 enzymatic activity, cytokine expression, and cell profiles, including cell counts, cell viability, DNA synthesis, and apoptosis, were measured in pokeweed mitogen (PWM)-activated CD4+CD26+ H9 Th1 cells with or without the DPP4 inhibitors, evogliptin and sitagliptin. PWM treatment alone strongly stimulated the expression of mDPP4 and cytokines such as interleukin (IL)-2, IL-10, tumor necrosis factor-alpha, interferon-gamma, IL-13, and granulocyte-macrophage colony stimulating factor in the CD4+CD26+ H9 Th1 cells. Evogliptin or sitagliptin treatment potently inhibited mDPP4 activity in a dose-dependent manner but did not affect either the cytokine profile or cell viability in PWM-activated CD4+CD26+ H9 Th1 cells. These results suggest that, following immune stimulation, Th1 cell signaling pathways for cytokine expression function normally after treatment with evogliptin or sitagliptin, which efficiently inhibit mDPP4 enzymatic activity in Th1 cells.
Keywords: DPP4, CD26, Evogliptin, Sitagliptin, Type 2 diabetes, Th1 cell-specific cytokines


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