ArticleJCI insight2022
Activated cholesterol metabolism is integral for innate macrophage responses by amplifying Myd88 signaling.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Single-Cell RNA-Sequencing Reveals Tumor Microenvironment Composition and Prior Therapy Modulate Response to Axl Inhibition.Cellular and molecular bioengineering · 2026Article
- Altered cholesterol immunometabolism activates the macrophage NLRP3-inflammasome in lung fibrosis.American journal of respiratory cell and molecular biology · 2026Article
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Single-cell transcriptomics reveal alveolar macrophage-specific responses in single-hit ozone exposure model in mice.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Busulfan resistance in AML is associated with changes in mitochondrial copy number and lipid metabolism.Scientific reports · 2026Article
- Single-cell RNA sequencing identifies M2-like macrophage polarization associated with mesenchymal stem cell treatment in a murine sepsis model.Biomolecules & biomedicine · 2026Article
- The relationship between CXC chemokines and cellular senescence: from mechanisms to therapy.Biogerontology · 2026Review
- Aromatic microbial metabolite hippuric acid enhances inflammatory responses in macrophages via TLR-MyD88 signaling and lipid remodeling.Cell reports · 2026Article
- RORα: a critical nexus in the crosstalk between cholesterol metabolism and macrophage polarization.Frontiers in immunology · 2026Review
- Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.Research square · 2025Article
- Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.bioRxiv : the preprint server for biology · 2025Article
- ApoE [-/-] CA1-overexpressing knock-in mice aggravated atherosclerosis by increasing M1 macrophages.Atherosclerosis plus · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Features of Gene Regulation in Violation of the Inflammatory Response of Monocyte-like Cells Bearing Mitochondrial Mutations Associated with Atherosclerosis.Current medicinal chemistry · 2025Article
- Inhibition of Toll-like Receptors Alters Macrophage Cholesterol Efflux and Foam Cell Formation.International journal of molecular sciences · 2024Article
- Supramolecular nanoarchitectonics of propionylated polyrotaxanes with bulky nitrobenzyl stoppers for light-triggered drug release.RSC advances · 2024Article
- Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet.Frontiers in nutrition · 2024Article
- Article
- Redox signaling in impaired cascades of wound healing: promising approach.Molecular biology reports · 2023Review
- Supermolecule-Drug Conjugates Based on Acid-Degradable Polyrotaxanes for pH-Dependent Intracellular Release of Doxorubicin.Molecules (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies have shown that cellular metabolism is tightly linked to the regulation of immune cells. Here, we show that activation of cholesterol metabolism, involving cholesterol uptake, synthesis, and autophagy/lipophagy, is integral to innate immune responses in macrophages. In particular, cholesterol accumulation within endosomes and lysosomes is a hallmark of the cellular cholesterol dynamics elicited by Toll-like receptor 4 activation and is required for amplification of myeloid differentiation primary response 88 (Myd88) signaling. Mechanistically, Myd88 binds cholesterol via its CLR recognition/interaction amino acid consensus domain, which promotes the protein's self-oligomerization. Moreover, a novel supramolecular compound, polyrotaxane (PRX), inhibited Myd88‑dependent inflammatory macrophage activation by decreasing endolysosomal cholesterol via promotion of cholesterol trafficking and efflux. PRX activated liver X receptor, which led to upregulation of ATP binding cassette transporter A1, thereby promoting cholesterol efflux. PRX also inhibited atherogenesis in Ldlr-/- mice. In humans, cholesterol levels in circulating monocytes correlated positively with the severity of atherosclerosis. These findings demonstrate that dynamic changes in cholesterol metabolism are mechanistically linked to Myd88‑dependent inflammatory programs in macrophages and support the notion that cellular cholesterol metabolism is integral to innate activation of macrophages and is a potential therapeutic and diagnostic target for inflammatory diseases.
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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.