The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses of microglia and astrocytes
Open accessAbstract
Liver X receptors (LXRs) are nuclear receptors previously identified to be important in lipid metabolism. Recent reports suggest that LXR agonists also exhibit anti-inflammatory properties in mouse models of atherosclerosis and contact dermatitis. In the present study, we investigated the effects of LXR agonists on mouse microglia and astrocytes. When chronically activated, these resident-CNS glia have been implicated in the pathology of neuroinflammatory disorders including multiple sclerosis (MS). Our studies demonstrated for the first time that LXR agonists inhibited the production of nitric oxide, the pro-inflammatory cytokines IL-1beta and IL-6 and the chemokine MCP-1 from LPS-stimulated microglia and astrocytes. Furthermore, LXR agonists inhibited LPS-induction of nuclear factor-kappa B (NF-kappaB) DNA-binding activity. These agonists also blocked LPS-induction of IkappaB-alpha protein degradation in microglia, suggesting a mechanism by which these agonists modulate NF-kappaB DNA-binding activity. These studies suggest that LXR agonists suppress the production of pro-inflammatory molecules by CNS glia, at least in part, by modulating NF-kappaB-signaling pathways. Retinoid X receptors (RXRs) physically interact with LXR receptors, and the resulting obligate heterodimer regulates the expression of LXR-responsive genes. Interestingly, a combination of LXR and RXR agonists additively suppressed the production of NO by microglia and astrocytes. Collectively, these studies suggest that LXR agonists may be effective in the treatment of neuroinflammatory diseases including MS.
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“In murine models of AD and neuroinflammation, studies of the effects of nuclear receptor agonists have been focused principally on their actions in astrocytes and microglia5678.”
From Neuronally-directed effects of RXR activation in a mouse model of Alzheimer’s disease (2017) · cites this paper as [5]
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Liver X receptor biology and pharmacology: new pathways, challenges and opportunities
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Retinoid X receptors: common heterodimerization partners with distinct functions
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Cytokine Signaling Modulates Blood-Brain Barrier Function
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Metadata
- Authors
- Zhang-Gandhi, C. X., & Drew, P. D.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Corresponding author
- Drew, Paul D.
- ORCID
- Drew, Paul D.
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 183
- Issue
- 1-2
- Pages
- 50-59
- ISSN
- 0165-5728 (ISSN-L)
- PMC
- PMC2080645
- OpenAlex
- W2034959869
- Cited by
- 117
- References
- 50
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 3 · 2019: 7 · 2018: 2 · 2017: 5 · 2016: 10 · 2015: 8 · 2014: 7 · 2013: 11 · 2012: 9
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 047546, NS42860, P30NS047546, R01NS042860)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- liver X receptor agonist, retinoid X receptor agonist, microglia, astrocytes, neuroinflammation, multiple sclerosis, NF-κB signaling, nitric oxide, IL-1β, interleukin-6, MCP-1, lipopolysaccharide stimulation, IκBα degradation, anti-inflammatory activity
- MeSH terms
- Liver X Receptors, Benzenesulfonamides, Analysis of Variance, Animals, Animals, Newborn, Astrocytes, Cell Survival, Cells, Cultured, Cerebral Cortex, DNA-Binding Proteins, Dose-Response Relationship, Drug, Drug Interactions, Fluorocarbons, Gene Expression Regulation, Hydrocarbons, Fluorinated, Lipopolysaccharides, Nitric Oxide, Nitroprusside, Sulfonamides, Cytokines, Microglia, Receptors, Cytoplasmic and Nuclear, Retinoid X Receptors, Mice, Orphan Nuclear Receptors
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