Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/108976
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Pulido Salgado, Marta | - |
dc.contributor.author | Vidal Taboada, José Manuel | - |
dc.contributor.author | García-Díaz Barriga, Gerardo | - |
dc.contributor.author | Serratosa i Serdà, Joan | - |
dc.contributor.author | Valente, Tony | - |
dc.contributor.author | Castillo, Paola | - |
dc.contributor.author | Matalonga, Jonathan | - |
dc.contributor.author | Straccia, Marco | - |
dc.contributor.author | Canals i Coll, Josep M. | - |
dc.contributor.author | Valledor Fernández, Annabel | - |
dc.contributor.author | Solà i Subirana, Carme | - |
dc.contributor.author | Saura Martí, Josep | - |
dc.date.accessioned | 2017-03-27T14:54:40Z | - |
dc.date.available | 2017-03-27T14:54:40Z | - |
dc.date.issued | 2017-03-16 | - |
dc.identifier.issn | 1742-2094 | - |
dc.identifier.uri | http://hdl.handle.net/2445/108976 | - |
dc.description.abstract | Background 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.extent | 20 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | BioMed Central | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1186/s12974-017-0834-5 | - |
dc.relation.ispartof | Journal of Neuroinflammation, 2017, vol. 14, num. 54 | - |
dc.relation.uri | https://doi.org/10.1186/s12974-017-0834-5 | - |
dc.rights | cc-by (c) Pulido Salgado et al., 2017 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Malalties neurodegeneratives | - |
dc.subject.classification | Encefalomielitis | - |
dc.subject.classification | Genètica mèdica | - |
dc.subject.classification | Inflamació | - |
dc.subject.classification | RNA | - |
dc.subject.other | Neurodegenerative Diseases | - |
dc.subject.other | Encephalomyelitis | - |
dc.subject.other | Medical genetics | - |
dc.subject.other | Inflammation | - |
dc.subject.other | RNA | - |
dc.title | Myeloid C/EBPβ deficiency reshapes microglial gene expression and is protective in experimental autoimmune encephalomyelitis | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 670527 | - |
dc.date.updated | 2017-03-27T14:54:40Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 28302135 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (ISGlobal) Articles publicats en revistes (Biomedicina) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
670527.pdf | 5.36 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License