Characterization of the effect of the GLUT-1 inhibitor BAY-876 on T cells and macrophages
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved..
Increased aerobic glycolysis is a metabolic hallmark of proinflammatory leukocytes including macrophages and T cells. To take up glucose from the environment and fuel glycolysis, activated leukocytes upregulate the glucose transporter GLUT1. The orally bioavailable selective GLUT1 inhibitor BAY-876 was developed primarily as an anti-tumor drug. Our study assessed its activity on activated macrophages and CD4+ T cells. BAY-876 significantly attenuated glucose uptake by cultured CD4+ T cells and macrophages by 41% and 15%, respectively. Extracellular flux analysis of activated CD4+ T cells in vitro showed that BAY-876 significantly decreases glycolytic proton flux rate and lactate production, effects that are accompanied by an increased oxidative phosphorylation-mediated ATP production rate, leaving intracellular ATP levels per cell unchanged. However, GLUT1 inhibition reduced CD4+ T cell proliferation without compromising cell viability and reduced IFN-γ secretion by 20%. Moreover, TNF secretion from macrophages was reduced by 27%. We conclude that GLUT1-specific inhibitors, like BAY-876, deserve further in vivo testing in a broad range of (auto-) inflammatory disease models.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:945 |
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| Enthalten in: |
European journal of pharmacology - 945(2023) vom: 15. Apr., Seite 175552 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Ziyi [VerfasserIn] |
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| Links: |
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| Themen: |
8L70Q75FXE |
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| Anmerkungen: |
Date Completed 21.03.2023 Date Revised 21.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2023.175552 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a Increased aerobic glycolysis is a metabolic hallmark of proinflammatory leukocytes including macrophages and T cells. To take up glucose from the environment and fuel glycolysis, activated leukocytes upregulate the glucose transporter GLUT1. The orally bioavailable selective GLUT1 inhibitor BAY-876 was developed primarily as an anti-tumor drug. Our study assessed its activity on activated macrophages and CD4+ T cells. BAY-876 significantly attenuated glucose uptake by cultured CD4+ T cells and macrophages by 41% and 15%, respectively. Extracellular flux analysis of activated CD4+ T cells in vitro showed that BAY-876 significantly decreases glycolytic proton flux rate and lactate production, effects that are accompanied by an increased oxidative phosphorylation-mediated ATP production rate, leaving intracellular ATP levels per cell unchanged. However, GLUT1 inhibition reduced CD4+ T cell proliferation without compromising cell viability and reduced IFN-γ secretion by 20%. Moreover, TNF secretion from macrophages was reduced by 27%. We conclude that GLUT1-specific inhibitors, like BAY-876, deserve further in vivo testing in a broad range of (auto-) inflammatory disease models | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a GLUT1 | |
| 650 | 4 | |a Glucose | |
| 650 | 4 | |a Glycolysis | |
| 650 | 4 | |a Immunometabolism | |
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| 700 | 1 | |a Eckstein, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Delgobo, Murilo |e verfasserin |4 aut | |
| 700 | 1 | |a Ramos, Gustavo |e verfasserin |4 aut | |
| 700 | 1 | |a Frantz, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Hofmann, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Gladow, Nadine |e verfasserin |4 aut | |
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