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Histone Deacetylation Inhibitors as Therapy Concept in Sepsis

1
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt/Main, 60590 Frankfurt, Germany
2
Fraunhofer–IME, Project Group Translational Medicine and Pharmacology (TMP), 60596 Frankfurt, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 346; https://doi.org/10.3390/ijms20020346
Received: 31 December 2018 / Revised: 11 January 2019 / Accepted: 12 January 2019 / Published: 16 January 2019
(This article belongs to the Special Issue Histone Deacetylase Inhibitors in Health and Disease)
Sepsis is characterized by dysregulated gene expression, provoking a hyper-inflammatory response occurring in parallel to a hypo-inflammatory reaction. This is often associated with multi-organ failure, leading to the patient’s death. Therefore, reprogramming of these pro- and anti-inflammatory, as well as immune-response genes which are involved in acute systemic inflammation, is a therapy approach to prevent organ failure and to improve sepsis outcomes. Considering epigenetic, i.e., reversible, modifications of chromatin, not altering the DNA sequence as one tool to adapt the expression profile, inhibition of factors mediating these changes is important. Acetylation of histones by histone acetyltransferases (HATs) and initiating an open-chromatin structure leading to its active transcription is counteracted by histone deacetylases (HDACs). Histone deacetylation triggers a compact nucleosome structure preventing active transcription. Hence, inhibiting the activity of HDACs by specific inhibitors can be used to restore the expression profile of the cells. It can be assumed that HDAC inhibitors will reduce the expression of pro-, as well as anti-inflammatory mediators, which blocks sepsis progression. However, decreased cytokine expression might also be unfavorable, because it can be associated with decreased bacterial clearance. View Full-Text
Keywords: HDAC; sepsis; epigenetic HDAC; sepsis; epigenetic
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MDPI and ACS Style

von Knethen, A.; Brüne, B. Histone Deacetylation Inhibitors as Therapy Concept in Sepsis. Int. J. Mol. Sci. 2019, 20, 346. https://doi.org/10.3390/ijms20020346

AMA Style

von Knethen A, Brüne B. Histone Deacetylation Inhibitors as Therapy Concept in Sepsis. International Journal of Molecular Sciences. 2019; 20(2):346. https://doi.org/10.3390/ijms20020346

Chicago/Turabian Style

von Knethen, Andreas; Brüne, Bernhard. 2019. "Histone Deacetylation Inhibitors as Therapy Concept in Sepsis" Int. J. Mol. Sci. 20, no. 2: 346. https://doi.org/10.3390/ijms20020346

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