ArticleMolecular medicine (Cambridge, Mass.)2018
Ligation of free HMGB1 to TLR2 in the absence of ligand is negatively regulated by the C-terminal tail domain.
Article in Molecular medicine (Cambridge, Mass.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Engineered HMGB1 construct with tandem Box B domains promotes tissue regeneration without potential for inflammation.iScience · 2026Article
- The Role of the HMGB1 C-Terminal Domain in Epithelial-Mesenchymal Transition and Invasion in 2D and 3D MDA-MB-231 Breast Cancer Models.International journal of molecular sciences · 2026Article
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
- HMGB1/RAGE axis in tumor development: unraveling its significance.Frontiers in oncology · 2024Review
- MyD88-dependent Toll-like receptor 2 signaling modulates macrophage activation on lysate-adsorbed Teflon™ AF surfaces in anFrontiers in immunology · 2023Article
- Role of high mobility group box protein 1 in depression: A mechanistic and therapeutic perspective.World journal of psychiatry · 2022Review
- Transcriptomic Profiling Reveals That HMGB1 Induces Macrophage Polarization Different from Classical M1.Biomolecules · 2022Article
- RNA-seq Analysis of Peri-Implant Tissue Shows Differences in Immune, Notch, Wnt, and Angiogenesis Pathways in Aged Versus Young Mice.JBMR plus · 2021Article
- Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming.Cell metabolism · 2021Article
- Neuroinflammation in neurological disorders: pharmacotherapeutic targets from bench to bedside.Metabolic brain disease · 2021Review
- Toll-like receptor 2 activation and up-regulation by high mobility group box-1 contribute to post-operative neuroinflammation and cognitive dysfunction in mice.Journal of neurochemistry · 2021Article
- Crosstalk Between Intestinal Serotonergic System and Pattern Recognition Receptors on the Microbiota-Gut-Brain Axis.Frontiers in endocrinology · 2021Review
- Nucleotide-Binding Oligomerization Domain-Like Receptor 3 Deficiency Attenuated Isoproterenol-Induced Cardiac Fibrosis via Reactive Oxygen Species/High Mobility Group Box 1 Protein Axis.Frontiers in cell and developmental biology · 2020Article
- Cleavage of HMGB1 by Proteolytic Enzymes Associated with Inflammatory Conditions.Frontiers in immunology · 2020Article
- When Innate Immunity Meets Angiogenesis-The Role of Toll-Like Receptors in Endothelial Cells and Pulmonary Hypertension.Frontiers in medicine · 2020Review
- HMGB1 in Systemic Lupus Erythematosus.Frontiers in immunology · 2020Review
- Article
- Cross-Disease Innate Gene Signature: Emerging Diversity and Abundance in RA Comparing to SLE and SSc.Journal of immunology research · 2019Article
- HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction.Frontiers in neuroscience · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh mobility group box 1 (HMGB1) protein is a central endogenous inflammatory mediator contributing to the pathogenesis of several inflammatory disorders. HMGB1 interacts with toll-like receptors (TLRs) but contradictory evidence regarding its identity as a TLR2 ligand persists. The aim of this study was to investigate if highly purified HMGB1 interacts with TLR2 and if so, to determine the functional outcome.
methodsFull length or C-terminal truncated (Δ30) HMGB1 was purified from E.coli. Binding to TLR2-Fc was investigated by direct-ELISA. For the functional studies, proteins alone or in complex with peptidoglycan (PGN) were added to human embryonic kidney (HEK) cells transfected with functional TLR2, TLR 1/2 or TLR 2/6 dimers, macrophages, whole blood or peripheral blood mononuclear cells (PBMCs). Cytokine levels were determined by ELISA.
resultsIn vitro binding experiments revealed that Δ30 HMGB1, lacking the acidic tail domain, but not full length HMGB1 binds dose dependently to TLR2. Control experiments confirmed that the interaction was specific to TLR2 and could be inhibited by enzymatic digestion. Δ30 HMGB1 alone was unable to induce cytokine production via TLR2. However, full length HMGB1 and Δ30 HMGB1 formed complexes with PGN, a known TLR2 ligand, and synergistically potentiated the inflammatory response in PBMCs.
conclusionsWe have demonstrated that TLR2 is a receptor for HMGB1 and this binding is negatively regulated by the C-terminal tail. HMGB1 did not induce functional activation of TLR2 while both full length HMGB1 and Δ30 HMGB1 potentiated the inflammatory activities of the TLR2 ligand PGN. We hypothesize that Δ30 HMGB1 generated in vivo by enzymatic cleavage could act as an enhancer of TLR2-mediated inflammatory activities.
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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.