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Cited by 119Neuroinflammation and Neurodegeneration MechanismsNuclear Receptors and SignalingNF-κB Signaling Pathways

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

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Zhang-Gandhi, Cindy X., Drew, Paul D.·2007·Journal of Neuroimmunology
DOI 10.1016/j.jneuroim.2006.11.007PMC PMC2080645
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Abstract

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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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)
DOI
10.1016/j.jneuroim.2006.11.007
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
Licence
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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