ArticleMolecular medicine (Cambridge, Mass.)2013
Signaling of high mobility group box 1 (HMGB1) through toll-like receptor 4 in macrophages requires CD14.
Article in Molecular medicine (Cambridge, Mass.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
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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
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Stabilized adaptive states in microbiome-human integrated physiology: reframing health and chronic disease as symbiotic biological states.Frontiers in medicine · 2026Pooled it
- Effects of Dexmedetomidine Infusion on Inflammatory Responses and Injury of Lung Tidal Volume Changes during One-Lung Ventilation in Thoracoscopic Surgery: A Randomized Controlled Trial.Mediators of inflammation · 2018Trial
- Polydeoxyribonucleotide Attenuates Carbon Tetrachloride-Induced Acute Liver Injury Through ALife (Basel, Switzerland) · 2026Article
- HMGB1 as a danger signal in vascular remodeling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Review
- Single-Cell Transcriptomic Mapping of PD-L1/TLR4 Remodeling Informs Topical Immunoprevention Timing in Skin Carcinogenesis.bioRxiv : the preprint server for biology · 2026Article
- Biliary atresia: Rotavirus amplification of lipopolysaccharide/toll-like receptor 4 by mediating MMP7 upregulation through NF-κB.Pediatric research · 2025Article
- Hepatitis B virus promotes liver cancer by modulating the immune response to environmental carcinogens.Nature communications · 2025Article
- ROS anchor PAMPs-mediated extracellular HMGB1 self-association and its dimerization enhances pro-inflammatory signaling.Redox biology · 2025Article
- High Mobility Group Box 1 and Cardiovascular Diseases: Study of Act and Connect.Cardiovascular toxicology · 2024Review
- IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.Journal of neuroinflammation · 2024Article
- Reciprocal effect on lateral diffusion of receptor for advanced glycation endproducts and toll-like receptor 4 in the HEK293 cell membrane.European biophysics journal : EBJ · 2024Article
- In Silico Analyses Indicate a Lower Potency for Dimerization of TLR4/MD-2 as the Reason for the Lower Pathogenicity of Omicron Compared to Wild-Type Virus and Earlier SARS-CoV-2 Variants.International journal of molecular sciences · 2024Article
- IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.bioRxiv : the preprint server for biology · 2024Article
- Inhibition of TLR4 signalling to dampen joint inflammation in osteoarthritis.Rheumatology (Oxford, England) · 2024Review
- High mobility group box 1 (HMGB1) mediates nicotine-induced podocyte injury.Frontiers in pharmacology · 2024Article
- Crosstalk between myocardial autophagy and sterile inflammation in the development of heart failure.Autophagy reports · 2024Review
- "NO" Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD.Molecules (Basel, Switzerland) · 2023Review
- Article
- Exogenous heat shock proteins HSPA1A and HSPB1 regulate TNF-α, IL-1β and IL-10 secretion from monocytic cells.FEBS open bio · 2023Article
- Harnessing the Immunological Effects of Radiation to Improve Immunotherapies in Cancer.International journal of molecular sciences · 2023Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
High mobility group box 1 (HMGB1) is a DNA-binding protein that possesses cytokinelike, proinflammatory properties when released extracellularly in the C23-C45 disulfide form. HMGB1 also plays a key role as a mediator of acute and chronic inflammation in models of sterile injury. Although HMGB1 interacts with multiple pattern recognition receptors (PRRs), many of its effects in injury models occur through an interaction with toll-like receptor 4 (TLR4). HMGB1 interacts directly with the TLR4/myeloid differentiation protein 2 (MD2) complex, although the nature of this interaction remains unclear. We demonstrate that optimal HMGB1-dependent TLR4 activation in vitro requires the coreceptor CD14. TLR4 and MD2 are recruited into CD14-containing lipid rafts of RAW264.7 macrophages after stimulation with HMGB1, and TLR4 interacts closely with the lipid raft protein GM1. Furthermore, we show that HMGB1 stimulates tumor necrosis factor (TNF)-α release in WT but not in TLR4(-/-), CD14(-/-), TIR domain-containing adapter-inducing interferon-β (TRIF)(-/-) or myeloid differentiation primary response protein 88 (MyD88)(-/-) macrophages. HMGB1 induces the release of monocyte chemotactic protein 1 (MCP-1), interferon gamma-induced protein 10 (IP-10) and macrophage inflammatory protein 1α (MIP-1α) in a TLR4- and CD14-dependent manner. Thus, efficient recognition of HMGB1 by the TLR4/MD2 complex requires CD14.
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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.