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Article

LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response

Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum der Ruhr Universität Bochum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany
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Cells 2020, 9(10), 2282; https://doi.org/10.3390/cells9102282
Received: 10 September 2020 / Revised: 21 September 2020 / Accepted: 10 October 2020 / Published: 13 October 2020
Mitochondrial DNA (mtDNA) plays a vital role as a damage-associated molecular pattern in sepsis being able to shape the immune response. Since pathogen recognition receptors of innate immune cells are activated by demethylated DNA only, we set out to investigate the amount of DNA methyltransferase 1 (DNMT1) in mitochondria and the extent of mtDNA methylation in a human endotoxin model. Peripheral blood mononuclear cells of 20 healthy individuals were isolated from whole blood and stimulated with lipopolysaccharide (LPS) for 48 h. Subsequently, DNMT1 protein abundance was assessed in whole cells and a mitochondrial fraction. At the same time, methylation levels of mtDNA were quantified, and cytokine expression in the supernatant was measured. Despite increased cellular expression of DNMT1 after LPS stimulation, the degree of mtDNA methylation slightly decreased. Strikingly the mitochondrial protein abundance of DNMT1 was reduced by 50% in line with the lower degree of mtDNA methylation. Although only modest alterations were seen in the degree of mtDNA methylation, these strongly correlated with IL-6 and IL-10 expression. Our data may hint at a protein import problem for DNMT1 into the mitochondria under LPS stimulation and suggest a role of demethylated mtDNA in the regulation of the inflammatory immune response. View Full-Text
Keywords: sepsis; mitochondrial DNA; methylation sepsis; mitochondrial DNA; methylation
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MDPI and ACS Style

Koos, B.; Moderegger, E.L.; Rump, K.; Nowak, H.; Willemsen, K.; Holtkamp, C.; Thon, P.; Adamzik, M.; Rahmel, T. LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response. Cells 2020, 9, 2282. https://doi.org/10.3390/cells9102282

AMA Style

Koos B, Moderegger EL, Rump K, Nowak H, Willemsen K, Holtkamp C, Thon P, Adamzik M, Rahmel T. LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response. Cells. 2020; 9(10):2282. https://doi.org/10.3390/cells9102282

Chicago/Turabian Style

Koos, Björn, Eva L. Moderegger, Katharina Rump, Hartmuth Nowak, Katrin Willemsen, Caroline Holtkamp, Patrick Thon, Michael Adamzik, and Tim Rahmel. 2020. "LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response" Cells 9, no. 10: 2282. https://doi.org/10.3390/cells9102282

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