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Effects of the Antidiabetic Drugs Evogliptin and Sitagliptin on the Immune Function of CD26/DPP4 in Th1 Cells

Biomolecules & Therapeutics 2021년 29권 2호 p.154 ~ 165
윤현이, 성지현, Song Moon-Jung,
소속 상세정보
윤현이 ( Yoon Hyun-Yee ) - Korea University College of Life Sciences and Biotechnology Department of Biotechnology
성지현 ( Sung Ji-Hyun ) - Seoul National University Hospital Biomedical Research Institute
 ( Song Moon-Jung ) - Korea University College of Life Sciences and Biotechnology Department of Biotechnology

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.

키워드

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

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