Adenine is an anti-inflammatory metabolite found to be more abundant in M-CSF over GM-CSF-differentiated human macrophages.

Autor: Harber KJ; Department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands; Amsterdam Cardiovascular Sciences (ACS), Atherosclerosis & ischemic syndromes, Amsterdam, UMC, Netherlands; Amsterdam institute for Infection and Immunity (AII), Inflammatory diseases, Amsterdam, UMC, Netherlands; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, Netherlands., Nguyen TA; Department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands., Schomakers BV; Department of Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands; Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands., Heister DAF; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, Netherlands., de Vries HE; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, Netherlands; Amsterdam Neuroscience, Amsterdam, Netherlands., van Weeghel M; Department of Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands; Core Facility Metabolomics, Amsterdam UMC, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands. Electronic address: m.vanweeghel@amsterdamumc.nl., Van den Bossche J; Amsterdam Cardiovascular Sciences (ACS), Atherosclerosis & ischemic syndromes, Amsterdam, UMC, Netherlands; Amsterdam institute for Infection and Immunity (AII), Inflammatory diseases, Amsterdam, UMC, Netherlands; Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV, Amsterdam, Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam, UMC, Netherlands. Electronic address: j.vandenbossche@amsterdamumc.nl., de Winther MPJ; Department of Medical Biochemistry, Amsterdam UMC, University of Amsterdam, 1105 AZ, Amsterdam, Netherlands; Amsterdam Cardiovascular Sciences (ACS), Atherosclerosis & ischemic syndromes, Amsterdam, UMC, Netherlands; Amsterdam institute for Infection and Immunity (AII), Inflammatory diseases, Amsterdam, UMC, Netherlands. Electronic address: m.dewinther@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: Immunology letters [Immunol Lett] 2024 Feb; Vol. 265, pp. 23-30. Date of Electronic Publication: 2023 Dec 22.
DOI: 10.1016/j.imlet.2023.12.003
Abstrakt: Immunometabolism has been unveiled in the last decade to play a major role in controlling macrophage metabolism and inflammation. There has been a constant effort to understand the immunomodulating properties of regulated metabolites during inflammation with the aim of controlling and re-wiring aberrant macrophages in inflammatory diseases. M-CSF and GM-CSF-differentiated macrophages play a key role in mounting successful innate immune responses. When a resolution phase is not achieved however, GM-CSF macrophages contribute substantially more towards an adverse inflammatory milieu than M-CSF macrophages, consequently driving disease progression. Whether there are specific immunometabolites that determine the homoeostatic or inflammatory nature of M-CSF and GM-CSF-differentiated macrophages is still unknown. As such, we performed metabolomics analysis on LPS and IL-4-stimulated M-CSF and GM-CSF-differentiated human macrophages to identify differentially accumulating metabolites. Adenine was distinguished as a metabolite significantly higher in M-CSF-differentiated macrophages after both LPS or IL-4 stimulation. Human macrophages treated with adenine before LPS stimulation showed a reduction in inflammatory gene expression, cytokine secretion and surface marker expression. Adenine caused macrophages to become more quiescent by lowering glycolysis and OXPHOS which resulted in reduced ATP production. Moreover, typical metabolite changes seen during LPS-induced macrophage metabolic reprogramming were absent in the presence of adenine. Phosphorylation of metabolic signalling proteins AMPK, p38 MAPK and AKT were not responsible for the suppressed metabolic activity of adenine-treated macrophages. Altogether, in this study we highlight the immunomodulating capacity of adenine in human macrophages and its function in driving cellular quiescence.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan Van den Bossche reports financial support was provided by European Research Area Network on Cardiovascular Diseases. Jan Van den Bossche reports financial support was provided by Amsterdam Cardiovascular Sciences.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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