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2024-12-19

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cc-by (c) Glaría, E. et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/223475

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

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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.

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Matèries

Macròfags, Necrosi, Fetge

Matèries (anglès)

Macrophages, Necrosis, Liver

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Col·leccions

Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Institut de Neurociències (UBNeuro))

Citació

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. Liver X receptors and inflammatory-induced C/EBPβ selectively cooperate to control CD38 transcription. _Journal of Innate Immunity_. 2024. Vol. 17, núm. 1, pàgs. 56-77. [consulta: 24 de novembre de 2025]. ISSN: 1662-811X. [Disponible a: https://hdl.handle.net/2445/223475]

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