ArticleMolecular medicine (Cambridge, Mass.)2021
Redox modifications of cysteine residues regulate the cytokine activity of HMGB1.
Article in Molecular medicine (Cambridge, Mass.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- High mobility group box 1 and its post-translational modifications: Molecular mechanisms underlying neurodegenerative disease pathogenesis.Neural regeneration research · 2026Article
- HMGB1 Post-Translational Modifications in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Current Evidence, Emerging Mechanistic Concepts, and Unresolved Questions.International journal of molecular sciences · 2026Review
- The role of HMGB1 in vascular endothelial cells.Apoptosis : an international journal on programmed cell death · 2026Review
- Article
- Screening and Targeting the HMGB1/RAGE Axis via Proteomics to Alleviate Inflammatory Responses in aJournal of inflammation research · 2026Article
- HMGB1 dysregulation: a neuroimmune bridge to cognitive impairment in autoimmune thyroiditis.Frontiers in immunology · 2026Article
- HMGB1-enhanced autophagic degradation of E-cadherin facilitates mesothelial trans-differentiation and postoperative peritoneal adhesion.BMC gastroenterology · 2025Article
- HMGB1: a multifaceted mediator of cell death pathways in cardiovascular diseases.Apoptosis : an international journal on programmed cell death · 2025Review
- HMGB1: A New Target for Ischemic Stroke and Hemorrhagic Transformation.Translational stroke research · 2025Review
- Beyond the Toll-Like Receptor 4. Structure-Dependent Lipopolysaccharide Recognition Systems: How far are we?ChemMedChem · 2025Review
- ROS anchor PAMPs-mediated extracellular HMGB1 self-association and its dimerization enhances pro-inflammatory signaling.Redox biology · 2025Article
- Oxidative High Mobility Group Box-1 Accelerates Mitochondrial Transfer from Mesenchymal Stem Cells to Colorectal Cancer Cells Providing Cancer Cell Stemness.International journal of molecular sciences · 2025Article
- HMGB1: new biomarker and therapeutic target of autoimmune and autoinflammatory skin diseases.Frontiers in immunology · 2025Review
- High Mobility Group Box 1 (HMGB1): Molecular Signaling and Potential Therapeutic Strategies.Cells · 2024Review
- Role of Myeloperoxidase, Oxidative Stress, and Inflammation in Bronchopulmonary Dysplasia.Antioxidants (Basel, Switzerland) · 2024Review
- The Role of Alarmins in Osteoarthritis Pathogenesis: HMGB1, S100B and IL-33.International journal of molecular sciences · 2023Review
- Review
- Review
- High Mobility Group Box 1 (HMGB1): Potential Target in Sepsis-Associated Encephalopathy.Cells · 2023Review
- Interleukin-1 alpha and high mobility group box-1 secretion in polyinosinic:polycytidylic-induced colorectal cancer cells occur via RIPK1-dependent mechanism and participate in tumourigenesis.Journal of cell communication and signaling · 2023Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundHigh mobility group box 1 (HMGB1) is a nuclear protein with extracellular inflammatory cytokine activity. It is passively released during cell death and secreted by activated cells of many lineages. HMGB1 contains three conserved redox-sensitive cysteine residues: cysteines in position 23 and 45 (C23 and C45) can form an intramolecular disulfide bond, whereas C106 is unpaired and is essential for the interaction with Toll-Like Receptor (TLR) 4. However, a comprehensive characterization of the dynamic redox states of each cysteine residue and of their impacts on innate immune responses is lacking.
methodsPrimary human macrophages or murine macrophage-like RAW 264.7 cells were activated in cell cultures by redox-modified or point-mutated (C45A) recombinant HMGB1 preparations or by lipopolysaccharide (E. coli.0111: B4). Cellular phosphorylated NF-κB p65 subunit and subsequent TNF-α release were quantified by commercial enzyme-linked immunosorbent assays.
resultsCell cultures with primary human macrophages and RAW 264.7 cells demonstrated that fully reduced HMGB1 with all three cysteines expressing thiol side chains failed to generate phosphorylated NF-КB p65 subunit or TNF-α. Mild oxidation forming a C23-C45 disulfide bond, while leaving C106 with a thiol group, was required for HMGB1 to induce phosphorylated NF-КB p65 subunit and TNF-α production. The importance of a C23-C45 disulfide bond was confirmed by mutation of C45 to C45A HMGB1, which abolished the ability for cytokine induction. Further oxidation of the disulfide isoform also inactivated HMGB1.
conclusionsThese results reveal critical post-translational redox mechanisms that control the proinflammatory activity of HMGB1 and its inactivation during inflammation.
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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.