Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/108976
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dc.contributor.authorPulido Salgado, Marta-
dc.contributor.authorVidal Taboada, José Manuel-
dc.contributor.authorGarcia Diaz-Barriga, Gerardo-
dc.contributor.authorSerratosa i Serdà, Joan-
dc.contributor.authorValente, Tony-
dc.contributor.authorCastillo, Paola-
dc.contributor.authorMatalonga, Jonathan-
dc.contributor.authorStraccia, Marco-
dc.contributor.authorCanals i Coll, Josep M.-
dc.contributor.authorValledor Fernández, Annabel-
dc.contributor.authorSolà i Subirana, Carme-
dc.contributor.authorSaura Martí, Josep-
dc.date.accessioned2017-03-27T14:54:40Z-
dc.date.available2017-03-27T14:54:40Z-
dc.date.issued2017-03-16-
dc.identifier.issn1742-2094-
dc.identifier.urihttp://hdl.handle.net/2445/108976-
dc.description.abstractBackground CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo. In this study, we have tested this hypothesis by generating mice with myeloid C/EBPβ deficiency. Methods Mice with myeloid C/EBPβ deficiency were generated by crossing LysMCre and C/EBPβfl/fl mice. Primary microglial cultures from C/EBPβfl/fl and LysMCre-C/EBPβfl/fl mice were treated with lipopolysaccharide ± interferon γ (IFNγ) for 6 h, and gene expression was analyzed by RNA sequencing. Gene expression and C/EBPβ deletion were analyzed in vivo in microglia isolated from the brains of C/EBPβfl/fl and LysMCre-C/EBPβfl/fl mice treated systemically with lipolysaccharide or vehicle. Mice of LysMCre-C/EBPβfl/fl or control genotypes were subjected to experimental autoimmune encephalitis and analyzed for clinical signs for 52 days. One- or two-way ANOVA or Kruskal-Wallis with their appropriate post hoc tests were used. Results LysMCre-C/EBPβfl/fl mice showed an efficiency of C/EBPβ deletion in microglia of 100 and 90% in vitro and in vivo, respectively. These mice were devoid of female infertility, perinatal mortality and reduced lifespan that are associated to full C/EBPβ deficiency. Transcriptomic analysis of C/EBPβ-deficient primary microglia revealed C/EBPβ-dependent expression of 1068 genes, significantly enriched in inflammatory and innate immune responses GO terms. In vivo, microglial expression of the pro-inflammatory genes Cybb, Ptges, Il23a, Tnf and Csf3 induced by systemic lipopolysaccharide injection was also blunted by C/EBPβ deletion. CNS expression of C/EBPβ was upregulated in experimental autoimmune encephalitis and in multiple sclerosis samples. Finally, LysMCre-C/EBPβfl/fl mice showed robust attenuation of clinical signs in experimental autoimmune encephalitis. Conclusion This study provides new data that support a central role for C/EBPβ in the biology of activated microglia, and it offers proof of concept for the therapeutic potential of microglial C/EBPβ inhibition in multiple sclerosis.-
dc.format.extent20 p.-
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherBioMed Central-
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1186/s12974-017-0834-5-
dc.relation.ispartofJournal of Neuroinflammation, 2017, vol. 14, num. 54-
dc.relation.urihttps://doi.org/10.1186/s12974-017-0834-5-
dc.rightscc-by (c) Pulido Salgado et al., 2017-
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es-
dc.subject.classificationMalalties neurodegeneratives-
dc.subject.classificationEncefalomielitis-
dc.subject.classificationGenètica mèdica-
dc.subject.classificationInflamació-
dc.subject.classificationRNA-
dc.subject.otherNeurodegenerative diseases-
dc.subject.otherEncephalomyelitis-
dc.subject.otherMedical genetics-
dc.subject.otherInflammation-
dc.subject.otherRNA-
dc.titleMyeloid C/EBPβ deficiency reshapes microglial gene expression and is protective in experimental autoimmune encephalomyelitis-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.identifier.idgrec670527-
dc.date.updated2017-03-27T14:54:40Z-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (ISGlobal)

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