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

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

Immunity (2013-11-05)
Nuno Figueiredo, Angelo Chora, Helena Raquel, Nadja Pejanovic, Pedro Pereira, Björn Hartleben, Ana Neves-Costa, Catarina Moita, Dora Pedroso, Andreia Pinto, Sofia Marques, Hafeez Faridi, Paulo Costa, Raffaella Gozzelino, Jimmy L Zhao, Miguel P Soares, Margarida Gama-Carvalho, Jennifer Martinez, Qingshuo Zhang, Gerd Döring, Markus Grompe, J Pedro Simas, Tobias B Huber, David Baltimore, Vineet Gupta, Douglas R Green, João A Ferreira, Luis F Moita
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
抗LC3B ウサギ宿主抗体, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
エピルビシン 塩酸塩, ≥90% (HPLC)
エピルビシン 塩酸塩, European Pharmacopoeia (EP) Reference Standard