Reactive oxygen species (ROS) in macrophage activation and function in diabetes

Erika Rendra; Vladimir Riabov; Dieuwertje M Mossel; Tatyana Sevastyanova; Martin C Harmsen; Julia Kzhyshkowska

doi:10.1016/j.imbio.2018.11.010

Reactive oxygen species (ROS) in macrophage activation and function in diabetes

Immunobiology. 2019 Mar;224(2):242-253. doi: 10.1016/j.imbio.2018.11.010. Epub 2018 Dec 1.

Authors

Erika Rendra¹, Vladimir Riabov², Dieuwertje M Mossel³, Tatyana Sevastyanova², Martin C Harmsen⁴, Julia Kzhyshkowska⁵

Affiliations

¹ Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, the Netherlands; The Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Germany.
² The Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia.
³ The Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Germany.
⁴ Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, the Netherlands.
⁵ The Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Germany; Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk, Russia; Red Cross Blood Service Baden-Württemberg-Hessen, Germany. Electronic address: julia.kzhyshkowska@medma.uni-heidelberg.de.

PMID: 30739804
DOI: 10.1016/j.imbio.2018.11.010

Abstract

In a diabetic milieu high levels of reactive oxygen species (ROS) are induced. This contributes to the vascular complications of diabetes. Recent studies have shown that ROS formation is exacerbated in diabetic monocytes and macrophages due to a glycolytic metabolic shift. Macrophages are important players in the progression of diabetes and promote inflammation through the release of pro-inflammatory cytokines and proteases. Because ROS is an important mediator for the activation of pro-inflammatory signaling pathways, obesity and hyperglycemia-induced ROS production may favor induction of M1-like pro-inflammatory macrophages during diabetes onset and progression. ROS induces MAPK, STAT1, STAT6 and NFκB signaling, and interferes with macrophage differentiation via epigenetic (re)programming. Therefore, a comprehensive understanding of the impact of ROS on macrophage phenotype and function is needed in order to improve treatment of diabetes and its vascular complications. In the current comprehensive review, we dissect the role of ROS in macrophage polarization, and analyze how ROS production links metabolism and inflammation in diabetes and its complications. Finally, we discuss the contribution of ROS to the crosstalk between macrophages and endothelial cells in diabetic complications.

Keywords: Diabetes; Hyperglycemia; Inflammation; Macrophage; Metabolism; Obesity; Reactive oxygen species.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Diabetes Mellitus / drug therapy
Diabetes Mellitus / etiology*
Diabetes Mellitus / metabolism*
Disease Susceptibility
Energy Metabolism
Humans
Immunomodulation
Macrophage Activation / drug effects
Macrophage Activation / immunology*
Macrophages / drug effects
Macrophages / immunology*
Macrophages / metabolism*
Oxidative Stress / drug effects
Reactive Oxygen Species / metabolism
Signal Transduction

Substances

Reactive Oxygen Species