Effects of the antidiabetic drugs evogliptin and sitagliptin on the immune function of cd26/dpp4 in th1 cells

Hyunyee Yoon, Ji Hyun Sung, Moon Jung Song

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    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 cyto-kine 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.

    Original languageEnglish
    Pages (from-to)154-165
    Number of pages12
    JournalBiomolecules and Therapeutics
    Volume29
    Issue number2
    DOIs
    Publication statusPublished - 2021

    Bibliographical note

    Funding Information:
    This work was supported in part by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (No. 2020R1A2C2013827) and by the grants from Korea University and the Biomedical Research Institute, Seoul National University Hospital. Evogliptin and sitagliptin were provided by the Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital.

    Publisher Copyright:
    © 2021 The Korean Society of Applied Pharmacology.

    Keywords

    • CD26
    • DPP4
    • Evogliptin
    • Sitagliptin
    • Th1 cell-specific cytokines
    • Type 2 diabetes

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Medicine
    • Pharmacology
    • Drug Discovery

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