Back to Search Start Over

Anthracyclines induce DNA damage response-mediated protection against severe sepsis.

Authors :
Figueiredo N
Chora A
Raquel H
Pejanovic N
Pereira P
Hartleben B
Neves-Costa A
Moita C
Pedroso D
Pinto A
Marques S
Faridi H
Costa P
Gozzelino R
Zhao JL
Soares MP
Gama-Carvalho M
Martinez J
Zhang Q
Döring G
Grompe M
Simas JP
Huber TB
Baltimore D
Gupta V
Green DR
Ferreira JA
Moita LF
Source :
Immunity [Immunity] 2013 Nov 14; Vol. 39 (5), pp. 874-84. Date of Electronic Publication: 2013 Oct 31.
Publication Year :
2013

Abstract

Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options in addition to organ support measures. Here we show that the clinically approved group of anthracyclines acts therapeutically at a low dose regimen to confer robust protection against severe sepsis in mice. This salutary effect is strictly dependent on the activation of DNA damage response and autophagy pathways in the lung, as demonstrated by deletion of the ataxia telangiectasia mutated (Atm) or the autophagy-related protein 7 (Atg7) specifically in this organ. The protective effect of anthracyclines occurs irrespectively of pathogen burden, conferring disease tolerance to severe sepsis. These findings demonstrate that DNA damage responses, including the ATM and Fanconi Anemia pathways, are important modulators of immune responses and might be exploited to confer protection to inflammation-driven conditions, including severe sepsis.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4180
Volume :
39
Issue :
5
Database :
MEDLINE
Journal :
Immunity
Publication Type :
Academic Journal
Accession number :
24184056
Full Text :
https://doi.org/10.1016/j.immuni.2013.08.039