Histone deacetylase inhibitors impair antibacterial defenses of macrophages.

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Serval ID
serval:BIB_B919DFAC5DBD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Histone deacetylase inhibitors impair antibacterial defenses of macrophages.
Journal
Journal of Infectious Diseases
Author(s)
Mombelli M., Lugrin J., Rubino I., Chanson A.L., Giddey M., Calandra T., Roger T.
ISSN
1537-6613 (Electronic)
ISSN-L
0022-1899
Publication state
Published
Issued date
2011
Volume
204
Number
9
Pages
1367-1374
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Histone deacetylases (HDACs) control gene expression by deacetylating histones and nonhistone proteins. HDAC inhibitors (HDACi) are powerful anticancer drugs that exert anti-inflammatory and immunomodulatory activities. We recently reported a proof-of-concept study demonstrating that HDACi increase susceptibility to bacterial infections in vivo. Yet, still little is known about the effects of HDACi on antimicrobial innate immune defenses. Here we show that HDACi belonging to different chemical classes inhibit at multiple levels the response of macrophages to bacterial infection. HDACi reduce the phagocytosis and the killing of Escherichia coli and Staphylococcus aureus by macrophages. In line with these findings, HDACi decrease the expression of phagocytic receptors and inhibit bacteria-induced production of reactive oxygen and nitrogen species by macrophages. Consistently, HDACi impair the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits and inducible nitric oxide synthase. These data indicate that HDACi have a strong impact on critical antimicrobial defense mechanisms in macrophages.
Keywords
Animals, Escherichia coli/immunology, Female, Histone Deacetylase Inhibitors/pharmacology, Immunologic Factors/physiology, Macrophages/drug effects, Macrophages/immunology, Mice, Mice, Inbred BALB C, Microbial Viability, NADPH Oxidase/antagonists & inhibitors, Nitric Oxide Synthase Type II/antagonists & inhibitors, Phagocytosis/drug effects, Phagocytosis/immunology, Reactive Nitrogen Species/metabolism, Reactive Oxygen Species/metabolism, Staphylococcus aureus/immunology
Pubmed
Web of science
Open Access
Yes
Create date
12/01/2012 19:05
Last modification date
25/09/2019 6:10
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