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Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics

Sepsis has a complex pathophysiology in which both excessive and refractory inflammatory responses are hallmark features. Pro-inflammatory cytokine responses during the early stages are responsible for significant endothelial dysfunction, loss of endothelial integrity, and organ failure. In addition...

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Autores principales: Cross, Deborah, Drury, Ruth, Hill, Jennifer, Pollard, Andrew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591469/
https://www.ncbi.nlm.nih.gov/pubmed/31275313
http://dx.doi.org/10.3389/fimmu.2019.01363
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author Cross, Deborah
Drury, Ruth
Hill, Jennifer
Pollard, Andrew J.
author_facet Cross, Deborah
Drury, Ruth
Hill, Jennifer
Pollard, Andrew J.
author_sort Cross, Deborah
collection PubMed
description Sepsis has a complex pathophysiology in which both excessive and refractory inflammatory responses are hallmark features. Pro-inflammatory cytokine responses during the early stages are responsible for significant endothelial dysfunction, loss of endothelial integrity, and organ failure. In addition, it is now well-established that a substantial number of sepsis survivors experience ongoing immunological derangement and immunosuppression following a septic episode. The underpinning mechanisms of these phenomena are incompletely understood yet they contribute to a significant proportion of sepsis-associated mortality. Epigenetic mechanisms including DNA methylation, histone modifications, and non-coding RNAs, have an increasingly clear role in modulating inflammatory and other immunological processes. Recent evidence suggests epigenetic mechanisms are extensively perturbed as sepsis progresses, and particularly play a role in endothelial dysfunction and immunosuppression. Whilst therapeutic modulation of the epigenome is still in its infancy, there is substantial evidence from animal models that this approach could reap benefits. In this review, we summarize research elucidating the role of these mechanisms in several aspects of sepsis pathophysiology including tissue injury and immunosuppression. We also evaluate pre-clinical evidence for the use of “epi-therapies” in the treatment of poly-microbial sepsis.
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spelling pubmed-65914692019-07-02 Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics Cross, Deborah Drury, Ruth Hill, Jennifer Pollard, Andrew J. Front Immunol Immunology Sepsis has a complex pathophysiology in which both excessive and refractory inflammatory responses are hallmark features. Pro-inflammatory cytokine responses during the early stages are responsible for significant endothelial dysfunction, loss of endothelial integrity, and organ failure. In addition, it is now well-established that a substantial number of sepsis survivors experience ongoing immunological derangement and immunosuppression following a septic episode. The underpinning mechanisms of these phenomena are incompletely understood yet they contribute to a significant proportion of sepsis-associated mortality. Epigenetic mechanisms including DNA methylation, histone modifications, and non-coding RNAs, have an increasingly clear role in modulating inflammatory and other immunological processes. Recent evidence suggests epigenetic mechanisms are extensively perturbed as sepsis progresses, and particularly play a role in endothelial dysfunction and immunosuppression. Whilst therapeutic modulation of the epigenome is still in its infancy, there is substantial evidence from animal models that this approach could reap benefits. In this review, we summarize research elucidating the role of these mechanisms in several aspects of sepsis pathophysiology including tissue injury and immunosuppression. We also evaluate pre-clinical evidence for the use of “epi-therapies” in the treatment of poly-microbial sepsis. Frontiers Media S.A. 2019-06-18 /pmc/articles/PMC6591469/ /pubmed/31275313 http://dx.doi.org/10.3389/fimmu.2019.01363 Text en Copyright © 2019 Cross, Drury, Hill and Pollard. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Cross, Deborah
Drury, Ruth
Hill, Jennifer
Pollard, Andrew J.
Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics
title Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics
title_full Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics
title_fullStr Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics
title_full_unstemmed Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics
title_short Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics
title_sort epigenetics in sepsis: understanding its role in endothelial dysfunction, immunosuppression, and potential therapeutics
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591469/
https://www.ncbi.nlm.nih.gov/pubmed/31275313
http://dx.doi.org/10.3389/fimmu.2019.01363
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