ArticleCellular and molecular life sciences : CMLS2015
Critical residues involved in Toll-like receptor 4 activation by cationic lipid nanocarriers are not located at the lipopolysaccharide-binding interface.
Article in Cellular and molecular life sciences : CMLS, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Sepsis Biomarkers in Evolution: Comparative Insights and the Promising Roles of MDW and Presepsin.Medicina (Kaunas, Lithuania) · 2026Review
- Ionizable lipid nanoparticles of mRNA vaccines elicit NF-κB and IRF responses through toll-like receptor 4.NPJ vaccines · 2025Article
- Low-inflammatory lipid nanoparticle-based mRNA vaccine elicits protective immunity against H5N1 influenza virus with reduced adverse reactions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Lipid nanoparticles as adjuvant of norovirus VLP vaccine augment cellular and humoral immune responses in a TLR9- and type I IFN-dependent pathway.Journal of virology · 2024Article
- Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications.Signal transduction and targeted therapy · 2024Review
- Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.Allergy · 2024Article
- Article
- Knife's edge: Balancing immunogenicity and reactogenicity in mRNA vaccines.Experimental & molecular medicine · 2023Review
- TLR4 and MD2 variation among horses with differential TNFα baseline concentrations and response to intravenous lipopolysaccharide infusion.Scientific reports · 2023Article
- Substituting racemic ionizable lipids with stereopure ionizable lipids can increase mRNA delivery.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Formulated Phospholipids as Non-Canonical TLR4 Agonists.Pharmaceutics · 2022Article
- Activation of Toll-like receptor 4 by Ebola virus-shed glycoprotein is direct and requires the internal fusion loop but not glycosylation.Cell reports · 2022Article
- Lipid-protein interactions regulating the canonical and the non-canonical NLRP3 inflammasome.Progress in lipid research · 2022Review
- Increased Interleukin 18-Dependent Immune Responses Are Associated With Myopericarditis After COVID-19 mRNA Vaccination.Frontiers in immunology · 2022Article
- Presepsin as Early Marker of Sepsis in Emergency Department: A Narrative Review.Medicina (Kaunas, Lithuania) · 2021Review
- Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety.Biomedicines · 2021Review
- Cationic Nanoparticle-Based Cancer Vaccines.Pharmaceutics · 2021Review
- Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses.Vaccines · 2020Article
- Toll-like Receptor 4 Stimulates Gene Expression via Smad2 Linker Region Phosphorylation in Vascular Smooth Muscle Cells.ACS pharmacology & translational science · 2020Article
- Nanotechnology as a Platform for the Development of Injectable Parenteral Formulations: A Comprehensive Review of the Know-Hows and State of the Art.Pharmaceutics · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
DiC14-amidine is a cationic lipid that was originally designed as a lipid nanocarrier for nucleic acid transport, and turned out to be a Toll-like receptor 4 (TLR4) agonist as well. We found that while E. coli lipopolysaccharide (LPS) is a TLR4 agonist in all species, diC14-amidine nanoliposomes are full agonists for human, mouse and cat receptors but weak horse agonists. Taking advantage of this unusual species specificity, we used chimeric constructs based on the human and horse sequences and identified two regions in the human TLR4 that modulate the agonist activity of diC14-amidine. Interestingly, these regions lie outside the known LPS-binding domain. Competition experiments also support our hypothesis that diC14-amidine interacts primarily with TLR4 hydrophobic crevices located at the edges of the TLR4/TLR4* dimerization interface. We have characterized potential binding modes using molecular docking analysis and suggest that diC14-amidine nanoliposomes activate TLR4 by facilitating its dimerization in a process that is myeloid differentiation 2 (MD-2)-dependent and cluster of differentiation 14 (CD14)-independent. Our data suggest that TLR4 may be activated through binding at different anchoring points, expanding the repertoire of TLR4 ligands to non-MD-2-binding lipids.
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Registered trials
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.