Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription

Introduction: Macrophages abundantly express liver X receptors (LXRs), which are ligand-dependent transcription factors and sensors of several cholesterol metabolites. In response to agonists, LXRs promote the expression of key lipid homeostasis regulators. Cross talk between LXRs and inflammatory s...

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Autores: Glaría Percaz, Estibaliz, Rodríguez Martínez, Pol, Font Díaz, Joan, Rosa, Juan Vladimir de la, Castrillo, Antonio, Crawshaw, Dylan J., Vidal Taboada, José Manuel, Saura Martí, Josep, Matalonga, Jonathan, Nunes Chini, Eduardo, Caelles Franch, Carme, Valledor Fernández, Annabel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/223475
Acceso en línea:https://hdl.handle.net/2445/223475
Access Level:acceso abierto
Palabra clave:Macròfags
Necrosi
Fetge
Macrophages
Necrosis
Liver
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repository_id_str
spelling Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcriptionGlaría Percaz, EstibalizRodríguez Martínez, PolFont Díaz, JoanRosa, Juan Vladimir de laCastrillo, AntonioCrawshaw, Dylan J.Vidal Taboada, José ManuelSaura Martí, JosepMatalonga, JonathanNunes Chini, EduardoCaelles Franch, CarmeValledor Fernández, AnnabelMacròfagsNecrosiFetgeMacrophagesNecrosisLiverIntroduction: Macrophages abundantly express liver X receptors (LXRs), which are ligand-dependent transcription factors and sensors of several cholesterol metabolites. In response to agonists, LXRs promote the expression of key lipid homeostasis regulators. Cross talk between LXRs and inflammatory signals exists in a cell type- and gene-specific manner. A common feature in the macrophage response to inflammatory mediators is the induction of CCAAT/enhancer-binding protein beta (C/EBPβ), a master transcriptional regulator and lineage-determining transcription factor in monocytes/macrophages. Methods: Quantitative real-time PCR in control and C/EBPβ-deficient macrophages was used to explore the role of C/EBPβ in the cross talk between inflammatory mediators and the macrophage response to pharmacological LXR activation. The functional interaction between C/EBPβ and LXRs on selected genomic regions was further characterized by chromatin-immunoprecipitation (ChIP) and gene reporter studies. Results: Whereas inflammatory signaling repressed several LXR-regulated genes involved in lipid metabolism, these effects were conserved after deletion of C/EBPβ. In contrast, inflammatory mediators and LXRs synergistically induced the expression of the multifunctional protein CD38 in a C/EBPβ-dependent manner. C/EBPβ and LXRs bound to several regions with enhancer activity upstream and within the mouse Cd38 gene and their functional cooperation in macrophages required intact binding sites for LXR and C/EBPβ. Conclusion: This study reveals positive cross talk between C/EBPβ and LXRs during the macrophage inflammatory response, which selectively impacts CD38 expression.Karger2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/223475Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1159/000543274Journal of Innate Immunity, 2024, vol. 17, num.1, p. 56-77https://doi.org/10.1159/000543274cc-by (c) Glaría, E. et al., 2024http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2234752026-05-27T06:46:51Z
dc.title.none.fl_str_mv Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
title Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
spellingShingle Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
Glaría Percaz, Estibaliz
Macròfags
Necrosi
Fetge
Macrophages
Necrosis
Liver
title_short Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
title_full Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
title_fullStr Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
title_full_unstemmed Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
title_sort Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
dc.creator.none.fl_str_mv Glaría Percaz, Estibaliz
Rodríguez Martínez, Pol
Font Díaz, Joan
Rosa, Juan Vladimir de la
Castrillo, Antonio
Crawshaw, Dylan J.
Vidal Taboada, José Manuel
Saura Martí, Josep
Matalonga, Jonathan
Nunes Chini, Eduardo
Caelles Franch, Carme
Valledor Fernández, Annabel
author Glaría Percaz, Estibaliz
author_facet Glaría Percaz, Estibaliz
Rodríguez Martínez, Pol
Font Díaz, Joan
Rosa, Juan Vladimir de la
Castrillo, Antonio
Crawshaw, Dylan J.
Vidal Taboada, José Manuel
Saura Martí, Josep
Matalonga, Jonathan
Nunes Chini, Eduardo
Caelles Franch, Carme
Valledor Fernández, Annabel
author_role author
author2 Rodríguez Martínez, Pol
Font Díaz, Joan
Rosa, Juan Vladimir de la
Castrillo, Antonio
Crawshaw, Dylan J.
Vidal Taboada, José Manuel
Saura Martí, Josep
Matalonga, Jonathan
Nunes Chini, Eduardo
Caelles Franch, Carme
Valledor Fernández, Annabel
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Macròfags
Necrosi
Fetge
Macrophages
Necrosis
Liver
topic Macròfags
Necrosi
Fetge
Macrophages
Necrosis
Liver
description Introduction: Macrophages abundantly express liver X receptors (LXRs), which are ligand-dependent transcription factors and sensors of several cholesterol metabolites. In response to agonists, LXRs promote the expression of key lipid homeostasis regulators. Cross talk between LXRs and inflammatory signals exists in a cell type- and gene-specific manner. A common feature in the macrophage response to inflammatory mediators is the induction of CCAAT/enhancer-binding protein beta (C/EBPβ), a master transcriptional regulator and lineage-determining transcription factor in monocytes/macrophages. Methods: Quantitative real-time PCR in control and C/EBPβ-deficient macrophages was used to explore the role of C/EBPβ in the cross talk between inflammatory mediators and the macrophage response to pharmacological LXR activation. The functional interaction between C/EBPβ and LXRs on selected genomic regions was further characterized by chromatin-immunoprecipitation (ChIP) and gene reporter studies. Results: Whereas inflammatory signaling repressed several LXR-regulated genes involved in lipid metabolism, these effects were conserved after deletion of C/EBPβ. In contrast, inflammatory mediators and LXRs synergistically induced the expression of the multifunctional protein CD38 in a C/EBPβ-dependent manner. C/EBPβ and LXRs bound to several regions with enhancer activity upstream and within the mouse Cd38 gene and their functional cooperation in macrophages required intact binding sites for LXR and C/EBPβ. Conclusion: This study reveals positive cross talk between C/EBPβ and LXRs during the macrophage inflammatory response, which selectively impacts CD38 expression.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/223475
url https://hdl.handle.net/2445/223475
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1159/000543274
Journal of Innate Immunity, 2024, vol. 17, num.1, p. 56-77
https://doi.org/10.1159/000543274
dc.rights.none.fl_str_mv cc-by (c) Glaría, E. et al., 2024
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Glaría, E. et al., 2024
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812455

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