Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/223475
Title: Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription
Author: Glaría Percaz, Estibaliz
Rodríguez Martínez, Pol
Font-Díaz, Joan
De la Rosa, Juan Vladimir
Castrillo, Antonio
Crawshaw, Dylan J.
Vidal Taboada, José Manuel
Saura Martí, Josep
Matalonga, Jonathan
Nunes Chini, Eduardo
Caelles Franch, Carme
Valledor Fernández, Annabel
Keywords: Macròfags
Necrosi
Fetge
Macrophages
Necrosis
Liver
Issue Date: 19-Dec-2024
Publisher: Karger
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1159/000543274
It is part of: Journal of Innate Immunity, 2024, vol. 17, num.1, p. 56-77
URI: https://hdl.handle.net/2445/223475
Related resource: https://doi.org/10.1159/000543274
ISSN: 1662-811X
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

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