Anthracyclines induce DNA damage response-mediated protection against severe sepsis
Standard
Anthracyclines induce DNA damage response-mediated protection against severe sepsis. / Figueiredo, Nuno; Chora, Angelo; Raquel, Helena; Pejanovic, Nadja; Pereira, Pedro; Hartleben, Björn; Neves-Costa, Ana; Moita, Catarina; Pedroso, Dora; Pinto, Andreia; Marques, Sofia; Faridi, Hafeez; Costa, Paulo; Gozzelino, Raffaella; Zhao, Jimmy L; Soares, Miguel P; Gama-Carvalho, Margarida; Martinez, Jennifer; Zhang, Qingshuo; Döring, Gerd; Grompe, Markus; Simas, J Pedro; Huber, Tobias B; Baltimore, David; Gupta, Vineet; Green, Douglas R; Ferreira, João A; Moita, Luis F.
in: IMMUNITY, Jahrgang 39, Nr. 5, 14.11.2013, S. 874-84.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Anthracyclines induce DNA damage response-mediated protection against severe sepsis
AU - Figueiredo, Nuno
AU - Chora, Angelo
AU - Raquel, Helena
AU - Pejanovic, Nadja
AU - Pereira, Pedro
AU - Hartleben, Björn
AU - Neves-Costa, Ana
AU - Moita, Catarina
AU - Pedroso, Dora
AU - Pinto, Andreia
AU - Marques, Sofia
AU - Faridi, Hafeez
AU - Costa, Paulo
AU - Gozzelino, Raffaella
AU - Zhao, Jimmy L
AU - Soares, Miguel P
AU - Gama-Carvalho, Margarida
AU - Martinez, Jennifer
AU - Zhang, Qingshuo
AU - Döring, Gerd
AU - Grompe, Markus
AU - Simas, J Pedro
AU - Huber, Tobias B
AU - Baltimore, David
AU - Gupta, Vineet
AU - Green, Douglas R
AU - Ferreira, João A
AU - Moita, Luis F
N1 - Copyright © 2013 Elsevier Inc. All rights reserved.
PY - 2013/11/14
Y1 - 2013/11/14
N2 - 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.
AB - 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.
KW - Adenoviridae Infections
KW - Animals
KW - Anthracyclines
KW - Anti-Bacterial Agents
KW - Ataxia Telangiectasia Mutated Proteins
KW - Autophagy-Related Protein 7
KW - Cecum
KW - DNA Damage
KW - DNA Repair
KW - Epirubicin
KW - Fanconi Anemia Complementation Group D2 Protein
KW - Inflammation
KW - Inflammation Mediators
KW - Injections, Intraperitoneal
KW - Lung
KW - Mice
KW - Mice, Inbred C57BL
KW - Microtubule-Associated Proteins
KW - Organ Specificity
KW - Peritonitis
KW - Respiratory Tract Infections
KW - Sepsis
KW - Shock, Septic
KW - Thienamycins
KW - Whole-Body Irradiation
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.immuni.2013.08.039
DO - 10.1016/j.immuni.2013.08.039
M3 - SCORING: Journal article
C2 - 24184056
VL - 39
SP - 874
EP - 884
JO - IMMUNITY
JF - IMMUNITY
SN - 1074-7613
IS - 5
ER -