ArticleScientific reports2018
Glucosylceramide modifies the LPS-induced inflammatory response in macrophages and the orientation of the LPS/TLR4 complex in silico.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Sphingolipids and Atherosclerosis.Current atherosclerosis reports · 2026Review
- Repairing Atp10D in C57Bl/6J mice restores protein expression but does not mitigate metabolic stress from high fat diet.Scientific reports · 2026Article
- Sphingolipid Metabolism: A Pathological Hub Linking Lipid Dysregulation and Chronic Inflammation in Atherosclerotic Cardiovascular Disease.Journal of inflammation research · 2026Review
- Rice-derived glucosylceramides activate innate immune responses in myeloid lineage differentiated dendritic cells via toll-like receptors 2 and 4.Journal of natural medicines · 2026Article
- UDP-Glucose Ceramide Glucosyltransferase Inhibition, Immune Cell Mediation, and Endometriosis Risk: A Mendelian Randomization Study.International journal of women's health · 2025Article
- Glycosphingolipids in Cardiovascular Disease: Insights from Molecular Mechanisms and Heart Failure Models.Biomolecules · 2024Review
- Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.Communications biology · 2024Article
- Glucosylceramide flippases contribute to cellular glucosylceramide homeostasis.Journal of lipid research · 2024Article
- Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease.Cell structure and function · 2024Article
- Deficiency of the lipid flippase ATP10A causes diet-induced dyslipidemia in female mice.Scientific reports · 2024Article
- Serine-/Cysteine-Based spJournal of medicinal chemistry · 2023Article
- Glycolipid Metabolite β-Glucosylceramide Is a Neutrophil Extracellular Trap-Inducing Ligand of Mincle Released during Bacterial Infection and Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- GBA1 and The Immune System: A Potential Role in Parkinson's Disease?Journal of Parkinson's disease · 2022Review
- Article
- Full-Atom Model of the Agonist LPS-Bound Toll-like Receptor 4 Dimer in a Membrane Environment.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Fighting Against Bacterial Lipopolysaccharide-Caused Infections through Molecular Dynamics Simulations: A Review.Journal of chemical information and modeling · 2021Review
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Multiplicity of Glycosphingolipid-Enriched Microdomain-Driven Immune Signaling.International journal of molecular sciences · 2021Review
- Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms.Journal of translational medicine · 2021Article
- Inhibiting TLR4 signaling by linarin for preventing inflammatory response in osteoarthritis.Aging · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor 4 (TLR4) is activated by bacterial lipopolysaccharide (LPS), which drives the production of proinflammatory cytokines. Earlier studies have indicated that cholesterol- and glycosphingolipid-rich subregions of the plasma membrane (lipid domains) are important for TLR4-mediated signaling. We report that inhibition of glucosylceramide (GluCer) synthase, which resulted in decreased concentrations of the glycosphingolipid GluCer in lipid domains, reduced the LPS-induced inflammatory response in both mouse and human macrophages. Atomistic molecular dynamics simulations of the TLR4 dimer complex (with and without LPS in its MD-2 binding pockets) in membranes (in the presence and absence of GluCer) showed that: (1) LPS induced a tilted orientation of TLR4 and increased dimer integrity; (2) GluCer did not affect the integrity of the LPS/TLR4 dimer but reduced the LPS-induced tilt; and (3) GluCer increased electrostatic interactions between the membrane and the TLR4 extracellular domain, which could potentially modulate the tilt. We also showed that GCS inhibition reduced the interaction between TLR4 and the intracellular adaptor protein Mal. We conclude that the GluCer-induced effects on LPS/TLR4 orientation may influence the signaling capabilities of the LPS/TLR4 complex by affecting its interaction with downstream signaling proteins.
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