ReviewFrontiers in immunology2020
TLR4 Signaling by Heme and the Role of Heme-Binding Blood Proteins.
Review 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 47 papers.
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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
47 citing papers in PubMed, 64 citations in OpenAlex.
- The Effects of Free Heme on Functional and Molecular Changes DuringFrontiers in immunology · 2022Trial
- Cerebrospinal Fluid Hemopexin as a Candidate Biomarker for Secondary Sepsis and In-Hospital Outcome After Spontaneous Intracerebral Hemorrhage: An Exploratory Translational Proteomics Study.Neurocritical care · 2026Article
- Conjugates of Heme and Intrinsically Disordered Peptides toward the Development of Synthetic Artificial Oxygen Carriers.Bioconjugate chemistry · 2026Article
- Hemoglobin inhibits fibroblast-to-cardiomyocyte reprogramming via TLR2/TLR4-dependent chromatin compaction.Molecular therapy. Nucleic acids · 2026Article
- Apohemoglobin-haptoglobin complex is a therapeutic against vaso-occlusive crisis: scavenging of hemoglobin and heme.Blood advances · 2026Article
- Galectin-3 Mediates Heme-Induced Multi-Organ Dysfunction by Modulating the Splenic Immune Microenvironment.Diseases (Basel, Switzerland) · 2026Article
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- Sensitive and specific methodology for detection of labile NO-ferroheme complexes in vitro and in blood.Redox biology · 2026Article
- Unravelling the Immunological Enigma of Sickle Cell Disease: Current Understanding and Future Directions.Immunology · 2026Review
- Free Fetal Haemoglobin in Severe Early-Onset Fetal Growth Restriction: A Prospective Multi-Centre Study.BJOG : an international journal of obstetrics and gynaecology · 2026Article
- The Role of the NF-κB Signaling Pathway in Atherosclerotic Plaque Rupture and Targeted Therapeutic Strategies.Biomedicines · 2026Review
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- Oxidized Cell-Free Hemoglobin Induces Mitochondrial Dysfunction by Activation of the Mitochondrial Permeability Transition Pore in the Pulmonary Microvasculature.Microcirculation (New York, N.Y. : 1994) · 2025Article
- Trained immunity causes myeloid cell hypercoagulability.Science advances · 2025Article
- Pro-Oxidative and Inflammatory Actions of Extracellular Hemoglobin and Heme: Molecular Events and Implications for Alzheimer's and Parkinson Disease.Biomolecules & therapeutics · 2025Review
- Inflammatory disease progression shapes nanoparticle biomolecular corona-mediated immune activation profiles.Nature communications · 2025Article
- Sub-chronic exposure to crude acetylene results in the development of deleterious cardio metabolic changes in Sprague Dawley rats.PloS one · 2025Article
- Stored RBC transfusions leads to the systemic inflammatory response syndrome in anemic murine neonates.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Phalloidin-PAINT: Enhanced quantitative nanoscale imaging of F-actin.Biophysical journal · 2024Article
- Role of microglia after subarachnoid hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors (TLRs), also known as pattern recognition receptors, respond to exogenous pathogens and to intrinsic danger signals released from damaged cells and tissues. The tetrapyrrole heme has been suggested to be an agonist for TLR4, the receptor for the pro-inflammatory bacterial component lipopolysaccharide (LPS), synonymous with endotoxin. Heme is a double-edged sword with contradictory functions. On the one hand, it has vital cellular functions as the prosthetic group of hemoproteins including hemoglobin, myoglobin, and cytochromes. On the other hand, if released from destabilized hemoproteins, non-protein bound or "free" heme can have pro-oxidant and pro-inflammatory effects, the mechanisms of which are not fully understood. In this review, the complex interactions between heme and TLR4 are discussed with a particular focus on the role of heme-binding serum proteins in handling extracellular heme and its impact on TLR4 signaling. Moreover, the role of heme as a direct and indirect trigger of TLR4 activation and species-specific differences in the regulation of heme-dependent TLR4 signaling are highlighted.
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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.