ArticleFrontiers in immunology2020
Identification of a Heme Activation Site on the MD-2/TLR4 Complex.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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
27 citing papers in PubMed, 40 citations in OpenAlex.
- GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular Glues.Journal of chemical information and modeling · 2026Article
- The mechanisms by which free heme exacerbates sepsis and the potential therapeutic targets.Frontiers in immunology · 2026Review
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular Glues.bioRxiv : the preprint server for biology · 2025Article
- HCAR2 is a novel receptor for heme.Blood advances · 2025Article
- B12 promotes gut dysbiosis and an inflammatory microenvironment that potentiatesbioRxiv : the preprint server for biology · 2025Article
- Transcriptomic atlas reveals organ-specific disease tolerance in sickle cell mice.Blood advances · 2025Article
- Unraveling the Protective Role of Oleocanthal and Its Oxidation Product, Oleocanthalic Acid, against Neuroinflammation.Antioxidants (Basel, Switzerland) · 2024Article
- Cell-Free Hemoglobin in the Pathophysiology of Trauma: A Scoping Review.Critical care explorations · 2024Article
- The clinical relevance of heme detoxification by the macrophage heme oxygenase system.Frontiers in immunology · 2024Review
- Endogenous Ligands of TLR4 in Microglia: Potential Targets for Related Neurological Diseases.Current drug targets · 2024Review
- Role of Small Molecule Ligands in IgE-Mediated Allergy.Current allergy and asthma reports · 2023Review
- Article
- The NLRP3 inflammasome fires up heme-induced inflammation in hemolytic conditions.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Shedding light on the molecular and regulatory mechanisms of TLR4 signaling in endothelial cells under physiological and inflamed conditions.Frontiers in immunology · 2023Review
- Novel aspects of sepsis pathophysiology: NETs, plasma glycoproteins, endotheliopathy and COVID-19.Journal of pharmacological sciences · 2022Review
- Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic.International journal of molecular sciences · 2022Review
- Hacking Commensal Bacteria to Consolidate the Adaptive Mucosal Immune Response in the Gut-Lung Axis: Future Possibilities for SARS-CoV-2 Protection.Biotech (Basel (Switzerland)) · 2022Review
- Article
- Potential Role of Soluble Toll-like Receptors 2 and 4 as Therapeutic Agents in Stroke and Brain Hemorrhage.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Myeloid differentiation factor-2 (MD-2) binds lipopolysaccharide (LPS) and initiates toll-like receptor-4 (TLR4) pro-inflammatory signaling. Heme also activates TLR4 signaling, but it is unknown if heme interacts with MD-2. Therefore, we examined MD-2 for a potential heme activation site. Heme-agarose and biotin-heme/streptavidin-agarose pulled down recombinant MD-2, which was inhibited by excess free heme. UV/visible spectroscopy confirmed MD-2-heme binding. To determine whether MD-2 was required for heme-mediated TLR4 signaling, HEK293 cells were transfected with MD-2, TLR4, CD14, and an NF-κB luciferase reporter, and then stimulated with heme or LPS. Heme or LPS treatment elicited robust reporter activity. Absence of MD-2, TLR4 or CD14 plasmid abolished NF-κB reporter responses to heme or LPS.
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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.