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 inf...
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| Format: | Article |
| Language: | English |
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Karger Publishers
2025-01-01
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| Series: | Journal of Innate Immunity |
| Online Access: | https://karger.com/article/doi/10.1159/000543274 |
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| author | Estibaliz Glaría Pol Rodríguez Martínez Joan Font-Díaz Juan Vladimir De la Rosa Antonio Castrillo Dylan J. Crawshaw Jose Manuel Vidal Taboada Josep Saura Jonathan Matalonga Eduardo Nunes Chini Carme Caelles Annabel F. Valledor |
| author_facet | Estibaliz Glaría Pol Rodríguez Martínez Joan Font-Díaz Juan Vladimir De la Rosa Antonio Castrillo Dylan J. Crawshaw Jose Manuel Vidal Taboada Josep Saura Jonathan Matalonga Eduardo Nunes Chini Carme Caelles Annabel F. Valledor |
| author_sort | Estibaliz Glaría |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-c0d3cd2842e04e02a1e89b011f59e040 |
| institution | Kabale University |
| issn | 1662-8128 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Journal of Innate Immunity |
| spelling | doaj-art-c0d3cd2842e04e02a1e89b011f59e0402025-08-20T03:49:41ZengKarger PublishersJournal of Innate Immunity1662-81282025-01-01171567710.1159/000543274Liver X Receptors and Inflammatory-Induced C/EBPβ Selectively Cooperate to Control CD38 TranscriptionEstibaliz GlaríaPol Rodríguez MartínezJoan Font-DíazJuan Vladimir De la RosaAntonio CastrilloDylan J. CrawshawJose Manuel Vidal TaboadaJosep SauraJonathan MatalongaEduardo Nunes ChiniCarme CaellesAnnabel F. Valledor 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.https://karger.com/article/doi/10.1159/000543274 |
| spellingShingle | Estibaliz Glaría Pol Rodríguez Martínez Joan Font-Díaz Juan Vladimir De la Rosa Antonio Castrillo Dylan J. Crawshaw Jose Manuel Vidal Taboada Josep Saura Jonathan Matalonga Eduardo Nunes Chini Carme Caelles Annabel F. Valledor Liver X Receptors and Inflammatory-Induced C/EBPβ Selectively Cooperate to Control CD38 Transcription Journal of Innate Immunity |
| title | 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_short | 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 |
| url | https://karger.com/article/doi/10.1159/000543274 |
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