ArticleMolecular endocrinology (Baltimore, Md.)2008
The nuclear receptor Rev-erbalpha is a liver X receptor (LXR) target gene driving a negative feedback loop on select LXR-induced pathways in human macrophages.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- Human IL10 gene repression by Rev-erbα ameliorates Mycobacterium tuberculosis clearance.The Journal of biological chemistry · 2013Trial
- Roles of circadian clocks in macrophage metabolism: implications in inflammation and metabolism of lipids, glucose, and amino acids.American journal of physiology. Endocrinology and metabolism · 2025Review
- The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development.Cell communication and signaling : CCS · 2025Review
- Role of circadian transcription factor REV-ERB in cardiovascular diseases: a review.Frontiers in cardiovascular medicine · 2025Review
- Endurance Training Inhibits the JAK2/STAT3 Pathway to Alleviate Sarcopenia.Physiological research · 2024Article
- Article
- Review
- The REV-ERB Nuclear Receptors: Timekeepers for the Core Clock Period and Metabolism.Endocrinology · 2023Review
- Article
- Ageing and Low-Level Chronic Inflammation: The Role of the Biological Clock.Antioxidants (Basel, Switzerland) · 2022Review
- Circadian Regulation and Clock-Controlled Mechanisms of Glycerophospholipid Metabolism from Neuronal Cells and Tissues to Fibroblasts.Molecular neurobiology · 2022Review
- Nuclear Receptors and Clock Components in Cardiovascular Diseases.International journal of molecular sciences · 2021Review
- Nuclear receptors, the aryl hydrocarbon receptor, and macrophage function.Molecular aspects of medicine · 2021Review
- Nuclear Receptors in the Control of the NLRP3 Inflammasome Pathway.Frontiers in endocrinology · 2021Review
- Targeting REV-ERBα for therapeutic purposes: promises and challenges.Theranostics · 2020Review
- Nutrient-sensitive transcription factors TFEB and TFE3 couple autophagy and metabolism to the peripheral clock.The EMBO journal · 2019Article
- Mycobacterium tuberculosis and macrophage nuclear receptors: What we do and don't know.Tuberculosis (Edinburgh, Scotland) · 2019Review
- Macrophage nuclear receptors: Emerging key players in infectious diseases.PLoS pathogens · 2019Review
- The Liver X Receptor Is Upregulated in Monocyte-Derived Macrophages and Modulates Inflammatory Cytokines Based on LXRMediators of inflammation · 2019Article
- Shift work cycle-induced alterations of circadian rhythms potentiate the effects of high-fat diet on inflammation and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A role of the nuclear receptor Rev-erbalpha in the regulation of transcription pathways involving other nuclear receptors is emerging. Indeed, Rev-erbalpha is a negative regulator of transcription by binding to overlapping response elements shared with various nuclear receptors, including the peroxisome proliferator-activated receptors and the retinoid-related orphan receptor alpha (RORalpha). Here, we show that Rev-erbalpha is expressed in primary human macrophages and that its expression is induced by synthetic ligands for the liver X receptors (LXRs), which control cholesterol homeostasis, inflammation, and the immune response in macrophages. LXRalpha binds to a specific response element in the human Rev-erbalpha promoter, thus inducing Rev-erbalpha transcriptional expression. Interestingly, Rev-erbalpha does not influence basal or LXR-regulated cholesterol homeostasis. However, Rev-erbalpha overexpression represses the induction of toll-like receptor (TLR)-4 by LXR agonists, whereas Rev-erbalpha silencing by short interfering RNA results in enhanced TLR-4 expression upon LXR activation. Electrophoretic mobility shift, chromatin immunoprecipitation, and transient transfection experiments demonstrate that Rev-erbalpha represses human TLR-4 promoter activity by binding as a monomer to a RevRE site overlapping with the LXR response element site in the TLR-4 promoter. These data identify Rev-erbalpha as a new LXR target gene, inhibiting LXR-induction of TLR-4 in a negative transcriptional feedback loop, but not cholesterol homeostasis gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.