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Anthracyclines induce DNA damage response-mediated protection against severe sepsis

2013Artigo científico Acesso restrito
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dc.contributor.authorFigueiredo, Nuno
dc.contributor.authorChora, Ângelo Ferreira
dc.contributor.authorRaquel, Maria Helena
dc.contributor.authorPejanovic, Nadja
dc.contributor.authorPereira, Pedro
dc.contributor.authorHartleben, Björn
dc.contributor.authorNeves-Costa, Ana
dc.contributor.authorMoita, Catarina
dc.contributor.authorPedroso, Dora
dc.contributor.authorPinto, Andreia
dc.contributor.authorMarques, Sofia
dc.contributor.authorFaridi, Hafeez
dc.contributor.authorCosta, Paulo M.
dc.contributor.authorGozzelino, Raffaella
dc.contributor.authorZhao, Jimmy L.
dc.contributor.authorSoares, Miguel P.
dc.contributor.authorGama-Carvalho, Margarida
dc.contributor.authorMartinez, Jennifer
dc.contributor.authorZhang, Qingshuo
dc.contributor.authorDöring, Gerd
dc.contributor.authorGrompe, Markus
dc.contributor.authorSimas, J Pedro
dc.contributor.authorHuber, Tobias B.
dc.contributor.authorBaltimore, David
dc.contributor.authorGupta, Vineet
dc.contributor.authorGreen, Douglas R.
dc.contributor.authorFerreira, João
dc.contributor.authorMoita, Luis
dc.date.accessioned2021-12-21T16:21:51Z
dc.date.available2021-12-21T16:21:51Z
dc.date.issued2013
dc.descriptionCopyright © 2013 Elsevier Inc. All rights reserved.pt_PT
dc.description.abstractSevere 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.pt_PT
dc.description.sponsorshipL.F.M. receives support from FLAD and FCT (grants PTDC/SAU-IMU/110303/2009, PTDC/SAU-MII/100780/2008, and PTDC/SAU-IMU/110303/2009), A.C. receives support from FCT (PTDC/SAU-IMU/110303/2009), J.A.F. receives support from a Gulbenkian grant (96526/2009), and P.P. is an FCT fellow (SFRH/BD/45502/2008).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationImmunity. 2013 Nov 14;39(5):874-884pt_PT
dc.identifier.doi10.1016/j.immuni.2013.08.039pt_PT
dc.identifier.eissn1097-4180
dc.identifier.issn1074-7613
dc.identifier.urihttp://hdl.handle.net/10451/50502
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationRole of ASF/SF2 and SRp20 in IL-1β secretion
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/immunitypt_PT
dc.titleAnthracyclines induce DNA damage response-mediated protection against severe sepsispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberPTDC/SAU-IMU/110303/2009
oaire.awardNumberPTDC/SAU-MII/100780/2008
oaire.awardNumberSFRH/BD/45502/2008
oaire.awardTitleRole of ASF/SF2 and SRp20 in IL-1β secretion
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-IMU%2F110303%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-MII%2F100780%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F45502%2F2008/PT
oaire.citation.endPage884pt_PT
oaire.citation.issue5pt_PT
oaire.citation.startPage874pt_PT
oaire.citation.titleImmunitypt_PT
oaire.citation.volume39pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamSFRH
person.familyNameLeitão Figueiredo
person.familyNameFerreira Chaves do Rosário Chora
person.familyNameRaquel
person.familyNameNeves Costa
person.familyNameFerreira Moita
person.familyNamePedroso
person.familyNamePinto
person.familyNameMarques
person.familyNameCosta
person.familyNameda Gama Carvalho
person.familyNameSimas
person.familyNameFerreira
person.familyNameMoita
person.givenNameNuno Filipe
person.givenNameÂngelo António
person.givenNameHelena
person.givenNameAna
person.givenNameCatarina Susana
person.givenNameDora
person.givenNameAndreia
person.givenNameSofia
person.givenNamePaulo Matos
person.givenNameMargarida
person.givenNameJ Pedro
person.givenNameJoão
person.givenNameLuis
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person.identifier.orcid0000-0003-0707-315X
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person.identifier.scopus-author-id24554088300
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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