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dc.creatorOliva Martín, María Josées
dc.creatorSánchez Abarca, Luis Ignacioes
dc.creatorRodhe, Johannaes
dc.creatorCarrillo Jiménez, Alejandroes
dc.creatorVlachos, Pinelopies
dc.creatorHerrera Carmona, Antonio Josées
dc.creatorGarcía Quintanilla, Albertoes
dc.creatorCaballero Velázquez, Teresaes
dc.creatorVenero Recio, José Luises
dc.date.accessioned2017-02-22T12:45:35Z
dc.date.available2017-02-22T12:45:35Z
dc.date.issued2016
dc.identifier.citationOliva Martín, M.J., Sánchez Abarca, L.I., Rodhe, J., Carrillo Jiménez, A., Vlachos, P., Herrera, A.J.,...,Venero Recio, J.L. (2016). Caspase-8 inhibition represses initial human monocyte activation in septic shock model. Oncotarget, 7 (25), 37456-37470.
dc.identifier.issn1949-2553es
dc.identifier.urihttp://hdl.handle.net/11441/54656
dc.description.abstractIn septic patients, the onset of septic shock occurs due to the over-activation of monocytes. We tested the therapeutic potential of directly targeting innate immune cell activation to limit the cytokine storm and downstream phases. We initially investigated whether caspase-8 could be an appropriate target given it has recently been shown to be involved in microglial activation. We found that LPS caused a mild increase in caspase-8 activity and that the caspase-8 inhibitor IETD-fmk partially decreased monocyte activation. Furthermore, caspase-8 inhibition induced necroptotic cell death of activated monocytes. Despite inducing necroptosis, caspase-8 inhibition reduced LPS-induced expression and release of IL-1β and IL-10. Thus, blocking monocyte activation has positive effects on both the pro and anti-inflammatory phases of septic shock. We also found that in primary mouse monocytes, caspase-8 inhibition did not reduce LPS-induced activation or induce necroptosis. On the other hand, broad caspase inhibitors, which have already been shown to improve survival in mouse models of sepsis, achieved both. Thus, given that monocyte activation can be regulated in humans via the inhibition of a single caspase, we propose that the therapeutic use of caspase-8 inhibitors could represent a more selective alternative that blocks both phases of septic shock at the source.es
dc.description.sponsorshipUnión Europea, Ministerio de Economía y Competitividad SAF2012-39029es
dc.description.sponsorshipUnión Europea, Ministerio de Economía y Competitividad SAF2015-64171Res
dc.description.sponsorshipEspaña,Junta de Andalucía P10-CTS-6494es
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherImpact Journalses
dc.relation.ispartofOncotarget, 7 (25), 37456-37470.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectsepsises
dc.subjectmonocytees
dc.subjectinflammationes
dc.subjectcaspase-8es
dc.subjectnecroptosises
dc.titleCaspase-8 inhibition represses initial human monocyte activation in septic shock modeles
dc.typeinfo:eu-repo/semantics/articlees
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessrightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Bioquímica y Biología Moleculares
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/SAF2012-39029es
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/SAF2015-64171Res
dc.relation.projectIDP10-CTS-6494es
dc.relation.publisherversionhttp://dx.doi.org/10.18632/oncotarget.9648es
dc.identifier.doi10.18632/oncotarget.9648es
idus.format.extent15 p.es
dc.journaltitleOncotargetes
dc.publication.volumen7es
dc.publication.issue25es
dc.publication.initialPage37456es
dc.publication.endPage37470es

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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as: Attribution-NonCommercial-NoDerivatives 4.0 Internacional