Epigenetics in sepsis: targeting histone deacetylases.

Details

Serval ID
serval:BIB_681D67C12F26
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Epigenetics in sepsis: targeting histone deacetylases.
Journal
International Journal of Antimicrobial Agents
Author(s)
Ciarlo E., Savva A., Roger T.
ISSN
1872-7913 (Electronic)
ISSN-L
0924-8579
Publication state
Published
Issued date
2013
Volume
42
Number
Suppl.
Pages
S8-S12
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Severe sepsis and septic shock are lethal complications of infection, characterised by dysregulated inflammatory and immune responses. Our understanding of the pathogenesis of sepsis has improved markedly in recent years, but unfortunately has not been translated into efficient treatment strategies. Epigenetic mechanisms such as covalent modification of histones by acetylation are master regulators of gene expression under physiological and pathological conditions, and strongly impact on inflammatory and host defence responses. Histone acetylation is controlled by histone acetyltransferases and histone deacetylases (HDACs), which affect gene expression also by targeting non-histone transcriptional regulators. Numerous HDAC inhibitors (HDACi) are being tested in clinical trials, primarily for the treatment of cancer. We performed the first comprehensive study of the impact of HDACi on innate immune responses in vitro and in vivo. We showed that HDACi act essentially as negative regulators of the expression of critical immune receptors and antimicrobial pathways in innate immune cells. In agreement, HDACi impaired phagocytosis and killing of bacteria by macrophages, and increased susceptibility to non-severe bacterial and fungal infections. Strikingly, proof-of-principle studies demonstrated that HDACi protect from lethal toxic shock and septic shock. Overall, our observations argue for a close monitoring of the immunological and infection status of patients treated with HDACi, especially immunocompromised cancer patients. They also support the concept of pharmacological inhibitors of HDACs as promising drugs to treat inflammatory diseases, including sepsis.
Pubmed
Web of science
Create date
26/07/2013 16:40
Last modification date
20/08/2019 14:23
Usage data