ArticleCirculation research2011
LXRα regulates macrophage arginase 1 through PU.1 and interferon regulatory factor 8.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 91 citations in OpenAlex.
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- The arginase-polyamine signaling axis in immune cells: Implications for immune modulation and host-pathogen interactions.iScience · 2026Review
- The role of interferon regulatory factors in atherosclerosis: from cell type-specific mechanisms to therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
- Integrated single-cell and bulk tissue analyses reveal distinct macrophage subtypes and a candidate prognostic signature in colorectal cancer: implications for tumor immune characterization.Frontiers in immunology · 2026Article
- Leucine Attenuates Osteoarthritis via mTORC1/LXRα-Mediated Macrophage Reprogramming and Rspo2/β-Catenin Axis Suppression.Cartilage · 2025Article
- Spi1 aggravates neuropathic pain by modulating Clec7a-mediated neuroinflammation and microglial phagocytosis.The journal of headache and pain · 2025Article
- Exploring the Roles of Liver X Receptors in Lipid Metabolism and Immunity in Atherosclerosis.Biomolecules · 2025Review
- The roles of arginases and arginine in immunity.Nature reviews. Immunology · 2025Review
- The role of interferon regulatory factors in atherosclerosis.Frontiers in cardiovascular medicine · 2025Review
- Sphingosine 1-phosphate receptor 1signaling in macrophages reduces atherosclerosis in LDL receptor-deficient mice.JCI insight · 2024Article
- Single-cell RNA-sequencing reveals a unique landscape of the tumor microenvironment in obesity-associated breast cancer.Oncogene · 2024Article
- Review
- Lipid droplet-associated hydrolase mobilizes stores of liver X receptor sterol ligands and protects against atherosclerosis.Nature communications · 2024Article
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- The role of efferocytosis-fueled macrophage metabolism in the resolution of inflammation.Immunological reviews · 2023Review
- Inhibition of LXR controls the polarization of human inflammatory macrophages through upregulation of MAFB.Cellular and molecular life sciences : CMLS · 2023Article
- LXR agonist improves peripheral neuropathy and modifies PNS immune cells in aged mice.Journal of neuroinflammation · 2022Article
- Cholesterol metabolism: a new molecular switch to control inflammation.Clinical science (London, England : 1979) · 2021Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
rationaleActivation of liver X receptors (LXRs) inhibits the progression of atherosclerosis and promotes regression of existing lesions. In addition, LXRα levels are high in regressive plaques. Macrophage arginase 1 (Arg1) expression is inversely correlated with atherosclerosis progression and is markedly decreased in foam cells within the lesion.
objectiveTo investigate LXRα regulation of Arg1 expression in cultured macrophages and atherosclerotic regressive lesions. METHODS AND
resultsWe found that Arg1 expression is enhanced in CD68+ cells from regressive versus progressive lesions in a murine aortic arch transplant model. In cultured macrophages, ligand-activated LXRα markedly enhances basal and interleukin-4-induced Arg1 mRNA and protein expression as well as promoter activity. This LXRα-enhanced Arg1 expression correlates with a reduction in nitric oxide levels. Moreover, Arg1 expression within regressive atherosclerotic plaques is LXRα-dependent, as enhanced expression of Arg1 in regressive lesions is impaired in LXRα-deficient CD68+ cells. LXRα does not bind to the Arg1 promoter but instead promotes the interaction between PU.1 and interferon regulatory factor (IRF)8 transcription factors and induces their binding of a novel composite element. Accordingly, knockdown of either IRF8 or PU.1 strongly impairs LXRα regulation of Arg1 expression in macrophage cells. Finally, we demonstrate that LXRα binds the IRF8 locus and its activation increases IRF8 mRNA and protein levels in these cells.
conclusionsThis work implicates Arg1 in atherosclerosis regression and identifies LXRα as a novel regulator of Arg1 and IRF8 in macrophages. Furthermore, it provides a unique molecular mechanism by which LXRα regulates macrophage target gene expression through PU.1 and IRF8.
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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.