Cited by 1,158Cholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular DiseasesPeroxisome Proliferator-Activated Receptors

Reciprocal regulation of inflammation and lipid metabolism by liver X receptors

Joseph, Sean B., Castrillo, Antonio, Laffitte, Bryan A., Mangelsdorf, David J., Tontonoz, Peter·2003·Nature Medicine

Abstract

Macrophages have important roles in both lipid metabolism and inflammation and are central to the pathogenesis of atherosclerosis. The liver X receptors (LXRs) are established mediators of lipid-inducible gene expression, but their role in inflammation and immunity is unknown. We demonstrate here that LXRs and their ligands are negative regulators of macrophage inflammatory gene expression. Transcriptional profiling of lipopolysaccharide (LPS)-induced macrophages reveals reciprocal LXR-dependent regulation of genes involved in lipid metabolism and the innate immune response. In vitro, LXR ligands inhibit the expression of inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase (COX)-2 and interleukin-6 (IL-6) in response to bacterial infection or LPS stimulation. In vivo, LXR agonists reduce inflammation in a model of contact dermatitis and inhibit inflammatory gene expression in the aortas of atherosclerotic mice. These findings identify LXRs as lipid-dependent regulators of inflammatory gene expression that may serve to link lipid metabolism and immune functions in macrophages.

Integrity signals

Registry

Crossref · 10.1038/nm820

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Joseph, S. B., Castrillo, A., Laffitte, B. A., Mangelsdorf, D. J., & Tontonoz, P.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Tontonoz, Peter
Venue
Nature Medicine
Published
2003-01-13
Volume
9
Issue
2
Pages
213-219
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W4230088158
Cited by
1,158
References
40
Citations by year
2026: 33 · 2025: 36 · 2024: 36 · 2023: 46 · 2022: 40 · 2021: 58 · 2020: 45 · 2019: 52 · 2018: 45 · 2017: 56 · 2016: 46 · 2015: 46 · 2014: 65 · 2013: 50 · 2012: 63
FWCI
51.45
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (HL 660881)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
liver X receptor, macrophages, inflammation, lipid metabolism, atherosclerosis, lipopolysaccharide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6, innate immunity, contact dermatitis, LXR agonists, inflammatory gene expression
MeSH terms
Animals, Cells, Cultured, Inflammation, Lipids, Lipopolysaccharides, Signal Transduction, NF-kappa B, Receptors, Cytoplasmic and Nuclear, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review