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

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초록

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. © 2021 The Korean Society of Applied Pharmacology.

키워드

CD26; DPP4; Evogliptin; Sitagliptin; Th1 cell-specific cytokines; Type 2 diabetes; antidiabetic agent; CD4 antigen; CD8 antigen; dipeptidyl peptidase IV; dipeptidyl peptidase IV inhibitor; evogliptin; gamma interferon; gelatinase B; interferon; interleukin 10; interleukin 13; interleukin 15; interleukin 17; interleukin 2; interleukin 7; messenger RNA; microsphere; sitagliptin; tumor necrosis factor; adult; apoptosis; Article; cell differentiation; cell viability; controlled study; cytokine production; cytotoxicity; DNA synthesis; enzyme activity; enzyme kinetics; enzyme linked immunosorbent assay; flow cytometry; gene expression; human; human cell; IC50; immune function test; immunostimulation; macrophage; protein expression; protein function; protein phosphorylation; signal transduction; Th17 cell; Th1 cell
제목
Effects of the antidiabetic drugs evogliptin and sitagliptin on the immune function of cd26/dpp4 in th1 cells
저자
Yoon, H.; Sung, J.H.; Song, M.J.
DOI
10.4062/biomolther.2020.150
발행일
2021-03
유형
Article
저널명
Biomolecules & Therapeutics
권
29
호
2
페이지
154 ~ 165