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Crosstalk between Epigenetic and Metabolic Mechanisms in Chronic Inflammation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 4179

Special Issue Editor


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Guest Editor
Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, 69117 Heidelberg, Germany
Interests: macrophages differentiation; macrophage metabolism and epigenetics; molecular mechanisms of chronic inflammation in cancer, diabetes, vascular complications, and tissue regeneration; macrophage biomarkers; biomaterials for macrophage drug delivery
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Special Issue Information

Dear colleagues,

Chronic inflammation is the cause for most life-threatening diseases that include cancer, diabetes and its vascular compilations, and neurodegeneration. Chronic inflammation, both systemic and local, can also result in delay in wound healing and implant failure. Epigenetic and metabolic mechanism are both critical for the detrimental programming of immune cells.

Our issue is dedicated to elucidation of the essential epigenetic and metabolic mechanism that controls inflammatory programming of differed cell types, and to identification of emerging hubs where the epigenetic and metabolic pathways interact with each other. Therefore, we invite submissions that cover interaction between glycolysis, fatty acid oxidation, oxidative protein phosphorylation, amino-acid metabolism, hypoxia and oxidative stress, genomic and mitochondrial DNA methylation, histone code, and miRNA. We aim to identify the promising pathways and critical molecules for therapeutic targeting to revert detrimental inflammatory programs in various cell types and restore homeostatic balance in tissue and organs.

Prof. Dr. Julia Kzhyshkowska
Guest Editor

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Keywords

  • diabetes
  • atherosclerosis
  • cancer
  • macrophages
  • T-cells
  • endothelial cells
  • epigenetic
  • mitochondria

Published Papers (1 paper)

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Research

19 pages, 1555 KiB  
Article
Hyperglycemia Induces Inflammatory Response of Human Macrophages to CD163-Mediated Scavenging of Hemoglobin-Haptoglobin Complexes
by Laura Matuschik, Vladimir Riabov, Christina Schmuttermaier, Tatyana Sevastyanova, Christel Weiss, Harald Klüter and Julia Kzhyshkowska
Int. J. Mol. Sci. 2022, 23(3), 1385; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031385 - 26 Jan 2022
Cited by 11 | Viewed by 3498
Abstract
Hyperglycemia, a hallmark of diabetes, can induce inflammatory programming of macrophages. The macrophage scavenger receptor CD163 internalizes and degrades hemoglobin-haptoglobin (Hb-Hp) complexes built due to intravascular hemolysis. Clinical studies have demonstrated a correlation between impaired scavenging of Hb-Hp complexes via CD163 and diabetic [...] Read more.
Hyperglycemia, a hallmark of diabetes, can induce inflammatory programming of macrophages. The macrophage scavenger receptor CD163 internalizes and degrades hemoglobin-haptoglobin (Hb-Hp) complexes built due to intravascular hemolysis. Clinical studies have demonstrated a correlation between impaired scavenging of Hb-Hp complexes via CD163 and diabetic vascular complications. Our aim was to identify whether hyperglycemia is able to amplify inflammation via Hb-Hp complex interactions with the immune system. M(IFNγ), M(IL-4), and control M0 macrophages were differentiated out of primary human monocytes in normo- (5 mM) and hyperglycemic (25 mM) conditions. CD163 gene expression was decreased 5.53 times in M(IFNγ) with a further decrease of 1.99 times in hyperglycemia. Hyperglycemia suppressed CD163 surface expression in M(IFNγ) (1.43 times). Flow cytometry demonstrated no impairment of Hb-Hp uptake in hyperglycemia. However, hyperglycemia induced an inflammatory response of M(IFNγ) to Hb-Hp1-1 and Hb-Hp2-2 uptake with different dynamics. Hb-Hp1-1 uptake stimulated IL-6 release (3.03 times) after 6 h but suppressed secretion (5.78 times) after 24 h. Contrarily, Hb-Hp2-2 uptake did not affect IL-6 release after 6h but increased secretion after 24 h (3.06 times). Our data show that hyperglycemia induces an inflammatory response of innate immune cells to Hb-Hp1-1 and Hb-Hp2-2 uptake, converting the silent Hb-Hp complex clearance that prevents vascular damage into an inflammatory process, hereby increasing the susceptibility of diabetic patients to vascular complications. Full article
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