ArticleCell death and differentiation2014
Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 151 papers.
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Who cites it
151 citing papers in PubMed, 233 citations in OpenAlex.
- Targeting macrophage ferritin heavy chain mitigates ferroptosis and lung injury in experimental acute respiratory distress syndrome.Nature communications · 2026Article
- Vagus nerve control of HMGB1 accessibility: a bioelectronic strategy for inflammation and pain.Bioelectronic medicine · 2026Review
- RAGE Signalling in Acute Inflammatory Disorders: Therapeutic Potential of Natural Products.Biomolecules · 2026Review
- Article
- Alveolar macrophage-neutrophil crosstalk in acute lung injury: mechanisms, feedback loops, and therapeutic opportunities.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Pyroptosis in endometritis: Molecular mechanisms, pathogenic roles, and therapeutic opportunities.iScience · 2026Review
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Identifying Crucial Genes Associated with Pyroptosis in Lupus Nephritis.Inflammation · 2026Article
- Targeted deletion of macrophage ferritin heavy chain protects from macrophage ferroptosis in acute respiratory distress syndrome.Research square · 2026Article
- Neutrophil extracellular traps and pyroptosis: a molecular nexus linking systemic autoimmune diseases to atherosclerosis.Frontiers in immunology · 2026Review
- A comparative analysis of HMGB1 and pCTS-L immunomodulatory properties in human peripheral blood mononuclear cells.Frontiers in immunology · 2026Article
- Pharmacological intervention of the HMGB1-pCTS-L axis to ameliorate inflammatory diseases.Frontiers in immunology · 2026Review
- Dendritic Polyglycerol Sulfate Reduces Inflammation Through Inhibition of the HMGB1/RAGE Axis in RAW 264.7 Macrophages.International journal of molecular sciences · 2025Article
- From mechanisms to markers: role of pyroptosis in revolutionizing thyroid cancer care.Cell death discovery · 2025Review
- Repurposing a Detrimental Antibody Epitope as Targeted Therapeutics for Sepsis and Rheumatoid Arthritis.Research square · 2025Article
- Direct interaction of HMGB1 with SARS-CoV-2 facilitates its infection via RAGE-dependent endocytosis.iScience · 2025Article
- Botulinum toxin type A inhibits microglia pyroptosis by suppressing Cblb-mediated degradation of Pdlim1 to attenuate neuropathic pain.The journal of headache and pain · 2025Article
- HMGB1: A New Target for Ischemic Stroke and Hemorrhagic Transformation.Translational stroke research · 2025Review
- Fucoidan reduces NET accumulation and alleviates chemotherapy-induced peripheral neuropathy via the gut-blood-DRG axis.Journal of neuroinflammation · 2025Article
- Targeting Hsp90α to inhibit HMGB1-mediated renal inflammation and fibrosis.Cell proliferation · 2025Article
91 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Macrophages can be activated and regulated by high-mobility group box 1 (HMGB1), a highly conserved nuclear protein. Inflammatory functions of HMGB1 are mediated by binding to cell surface receptors, including the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, TLR4, and TLR9. Pyroptosis is a caspase-1-dependent programmed cell death, which features rapid plasma membrane rupture, DNA fragmentation, and release of proinflammatory intracellular contents. Pyroptosis can be triggered by various stimuli, however, the mechanism underlying pyroptosis remains unclear. In this study, we identify a novel pathway of HMGB1-induced macrophage pyroptosis. We demonstrate that HMGB1, acting through RAGE and dynamin-dependent signaling, initiates HMGB1endocytosis, which in turn induces cell pyroptosis. The endocytosis of HMGB1 triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. We further confirm that HMGB1-induced macrophage pyroptosis also occurs in vivo during endotoxemia, suggesting a pathophysiological significance for this form of pyroptosis in the development of inflammation. These findings shed light on the regulatory role of ligand-receptor internalization in directing cell fate, which may have an important role in the progress of inflammation following infection and injury.
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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.