☆ 4.7 Review

The multifunctional protein HMGB1: 50 years of discovery

NATURE REVIEWS IMMUNOLOGY (2023)

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Article Gastroenterology & Hepatology

Combining ferroptosis induction with MDSC blockade renders primary tumours and metastases in liver sensitive to immune checkpoint blockade

Claire Conche et al.

Summary: Investigating the effect of ferroptosis in the tumour microenvironment, specifically focusing on liver cancer, to identify potential combinatory therapies. The study genetically altered GPx4 in mouse models for hepatocellular carcinoma and colorectal cancer to analyze the impact of ferroptosis on tumor cells and the immune response. The findings revealed a context-specific ferroptosis-induced immune response that could be used in the treatment of liver tumors and liver metastases.

GUT (2023)

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Article Cell Biology

The telomeric protein TERF2/TRF2 impairs HMGB1-driven autophagy

Sara Iachettini et al.

Summary: TERF2 is a telomeric protein that plays a crucial role in tumor formation and progression. This study uncovers a novel function of TERF2 in regulating the autophagic process and reveals its interaction with HMGB1 as functional for protein localization.

AUTOPHAGY (2023)

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Article Gastroenterology & Hepatology

Hypoxic ASCs-derived Exosomes Attenuate Colitis by Regulating Macrophage Polarization via miR-216a-5p/HMGB1 Axis

Wenwei Qian et al.

Summary: In this study, it was found that exosomal miR-216a-5p released from hypoxia-preconditioned adipose-derived stem cells (ASCs) exhibited higher therapeutic efficacy than normal exosomes (NExos) in experimental colitis by promoting the M2 macrophage phenotype. This suggests that hypoxia preconditioning may be a promising approach to optimize the function of ASC-derived exosomes.

INFLAMMATORY BOWEL DISEASES (2023)

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Article Peripheral Vascular Disease

Peritumoral B cells drive proangiogenic responses in HMGB1-enriched esophageal squamous cell carcinoma

Ngar Woon Kam et al.

Summary: Different functions and profiles of B-cell subsets in various cancers have been reported. In esophageal squamous cell carcinoma (ESCC), proliferating B cells are predominantly found in the peritumoral region with high expression of HMGB1. Cancer-derived HMGB1 modulates B cells to promote angiogenesis in ESCC microenvironment.

ANGIOGENESIS (2022)

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Article Oncology

Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization

Zhuang Li et al.

Summary: This study demonstrated that enhanced secretory autophagy in GB facilitates M1-like polarization of TAMs to enhance TMZ sensitivity of GB cells. HMGB1 acts as a key regulator in the crosstalk between GB cells and tumor-suppressive M1-like TAMs in GB microenvironment and may be considered as an adjuvant for the chemotherapeutic agent TMZ.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2022)

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Article Immunology

TIRAP drives myelosuppression through an Ifnγ-Hmgb1 axis that disrupts the endothelial niche in mice

Aparna Gopal et al.

Summary: This study uncovers a novel role for TIRAP in driving bone marrow failure, which is mediated by the up-regulation of Ifn γ and the subsequent disruption of the bone marrow endothelial niche. Additionally, this study reveals the inhibitory role of Ifn γ in the transformation of MDS to acute leukemia.

JOURNAL OF EXPERIMENTAL MEDICINE (2022)

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Article Immunology

HMGB1-Mediated Neutrophil Extracellular Trap Formation Exacerbates Intestinal Ischemia/Reperfusion-Induced Acute Lung Injury

YaQing Zhan et al.

Summary: The influx of activated neutrophils into the lungs is a histopathologic hallmark of acute lung injury (ALI) after intestinal ischemia/reperfusion (I/R). Neutrophils can release cytotoxic neutrophil extracellular traps (NETs), while high-mobility group protein B1 (HMGB1) released from necroptotic enterocytes plays a crucial role in inducing NETosis and causing ALI. Targeting NETosis and the HMGB1 pathway could be effective therapeutic strategies to minimize ALI induced by intestinal I/R.

JOURNAL OF IMMUNOLOGY (2022)

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Article Multidisciplinary Sciences

Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies

Mari Kamiya et al.

Summary: Muscle cell death in polymyositis is induced by CD8(+) cytotoxic T lymphocytes. Inhibition of necroptosis in muscle cells could be a promising strategy for treating polymyositis and suppressing muscle injury and inflammation.

NATURE COMMUNICATIONS (2022)

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Article Cardiac & Cardiovascular Systems

HMGB1-Promoted Neutrophil Extracellular Traps Contribute to Cardiac Diastolic Dysfunction in Mice

Xin-Lin Zhang et al.

Summary: This study found elevated levels of circulating neutrophils and NETs markers in patients and mice with HFpEF, as well as increased cardiac neutrophils and NETs formation. HMGB1 inhibition and SGLT2 inhibitors can reduce NET formation, alleviate inflammation, and improve cardiac function.

JOURNAL OF THE AMERICAN HEART ASSOCIATION (2022)

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Article Cell Biology

Monoclonal antibodies capable of binding SARS-CoV-2 spike protein receptor-binding motif specifically prevent GM-CSF induction

Xiaoling Qiang et al.

Summary: SARS-CoV-2 uses spike protein to bind ACE2 for viral entry, and vaccines targeting spike protein may prevent viral infection. Specific antibodies can block virus-ACE2 interaction and reduce inflammatory responses, suggesting a potential anti-inflammatory mechanism for spike-based vaccines.

JOURNAL OF LEUKOCYTE BIOLOGY (2022)

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Review Biochemistry & Molecular Biology

The mechanism of HMGB1 secretion and release

Ruochan Chen et al.

Summary: Inflammation-promoting nuclear protein HMGB1 can be targeted for controlling immune response in diseases linked to excessive inflammation. This article reviews the mechanisms of HMGB1 release and discusses its potential as a therapeutic target for inflammatory diseases and tissue damage.

EXPERIMENTAL AND MOLECULAR MEDICINE (2022)

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Article Biology

Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death

Jazlyn P. Borges et al.

Summary: Glycine protects cells against rupture by targeting NINJ1, a newly identified executioner of plasma membrane rupture. Glycine prevents NINJ1 clustering and preserves cellular integrity, providing a mechanism for glycine-mediated cytoprotection.

ELIFE (2022)

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Article Immunology

The HMGB1 (C106A) mutation inhibits IL-10-producing CD19hiFcγRIIbhi B cell expansion by suppressing STAT3 activation in mice

Mengru Liu et al.

Summary: Regulatory B cells play important roles in inflammation and autoimmune diseases. The protein HMGB1 is involved in the expansion and immunosuppressive function of CD19(hi) Fc gamma RIIb(hi) B cells.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Multidisciplinary Sciences

Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias

Yu-Chen Yen et al.

Summary: This study presents cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The binding poses of these chemokines are different from those established for CXCR4 and observed in other receptor-chemokine complexes. These structures, together with functional studies, provide insights into the ligand-binding promiscuity of ACKR3, its inability to couple to G proteins, and its bias towards beta-arrestin, laying the foundation for understanding the physiological interplay of ACKR3 with other GPCRs.

SCIENCE ADVANCES (2022)

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Article Cell Biology

Cytosolic HMGB1 Mediates LPS-Induced Autophagy in Microglia by Interacting with NOD2 and Suppresses Its Proinflammatory Function

Seung-Woo Kim et al.

Summary: The study found that HMGB1 plays a critical role in mediating NOD2-induced autophagy in microglia. Cytoplasmic accumulation of HMGB1 activates a cell-autonomous pro-autophagic pathway, while extracellular secretion of HMGB1 activates a cell-autonomous pro-inflammatory pathway.

CELLS (2022)

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Article Critical Care Medicine

CARDIOPULMONARY BYPASS-DERIVED PLASMA EXOSOMAL HMGB1 CONTRIBUTES TO ALVEOLAR EPITHELIAL CELL NECROPTOSIS VIA mtDNA/CGAS/STING PATHWAY

Yupeng Zhao et al.

Summary: This study explored the role of exosomal HMGB1 and cytoplasmic mtDNA in AEC necroptosis during acute lung injury induced by cardiopulmonary bypass (CPB). The results demonstrated that plasma exosomal HMGB1 released after CPB contributed to AEC necroptosis through the mtDNA/cGAS/STING pathway. These findings provide new insights into the pathogenesis of ALI and suggest potential therapeutic targets for its treatment.

SHOCK (2022)

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Article Orthopedics

Neutralization of HMGB1 improves fracture healing and γδ T lymphocyte counts at the fracture site in a polytrauma rat model

Preeti J. Muire et al.

Summary: This study investigates the detrimental effect of excess release of high mobility group box 1 (HMGB1) molecules on immune responses and fracture healing in polytrauma patients. The results suggest that neutralizing HMGB1 can improve fracture healing in these patients, with a potential role of a subset of T cells in the process.

JOURNAL OF EXPERIMENTAL ORTHOPAEDICS (2022)

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Review Immunology

Immune ageing at single-cell resolution

Denis A. Mogilenko et al.

Summary: Studying ageing at the single-cell level has provided a greater understanding of the heterogeneity and dynamic nature of immune cell ageing, as well as the impact of age-associated tissue remodelling on the immune system. The widespread application of single-cell techniques has enabled substantial progress in our understanding of the ageing immune system.

NATURE REVIEWS IMMUNOLOGY (2022)

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Article Cell Biology

Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inflammation

Zhen Wang et al.

Summary: This study reveals a novel autophagy mechanism in the pathogenesis of psoriasis, indicating the pivotal role of HMGB1-associated autosecretion in cutaneous inflammation.

AUTOPHAGY (2021)

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Article Cell Biology

Secretory autophagy machinery and vesicular trafficking are involved in HMGB1 secretion

Young Hun Kim et al.

Summary: The study showed that stress-inducible protein HSP90AA1 and other proteins regulate the translocation and secretion of HMGB1, impacting inflammation and immune response. Additionally, secretory autophagy and multivesicular body formation play a role in mediating HMGB1 secretion.

AUTOPHAGY (2021)

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Article Biochemistry & Molecular Biology

Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

Jin Wei et al.

Summary: Identification of essential host genes for SARS-CoV-2 infection, including ACE2 and Cathepsin L, and the discovery of pro-viral genes and pathways specific to SARS lineage and pan-coronavirus provide potential therapeutic targets and insights into pathogenesis of COVID-19. Small-molecule antagonists of these gene products inhibited SARS-CoV-2 infection across species, highlighting their conserved role in susceptibility to highly pathogenic CoVs.

CELL (2021)

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Article Environmental Sciences

HMGB1 could restrict 1,3-β-glucan induced mice lung inflammation by affecting Beclin1 and Bcl2 interaction and promoting the autophagy of epithelial cells

Xinning Zeng et al.

Summary: Maintaining the homeostasis of epithelial cells is crucial for defending against exogenous fungi invasion. HMGB1-dependent autophagy plays a critical role in 1,3-beta-glucan induced lung inflammation. Silencing HMGB1 may exacerbate 1,3-beta-glucan induced lung inflammation, whereas ubiquitination of Beclin1 could be a key regulatory mechanism of HMGB1 on autophagy.

ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY (2021)

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Article Multidisciplinary Sciences

NINJ1 mediates plasma membrane rupture during lytic cell death

Nobuhiko Kayagaki et al.

Summary: Plasma membrane rupture is a cataclysmic event in lytic cell death, releasing damage-associated molecular patterns to propagate the inflammatory response. NINJ1 protein plays an essential role in inducing PMR, with Ninj1-deficient macrophages showing impaired release of intracellular proteins and distinctive ballooned morphology. This study overturns the long-held belief that cell death-related PMR is a passive event, highlighting the active role of NINJ1 in mediating PMR.

NATURE (2021)

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Article Cardiac & Cardiovascular Systems

Correlation of blood high mobility group box-1 protein with mortality of patients with sepsis: A meta-analysis

Jingjing Cai et al.

Summary: Initial high blood HMGB-1 levels are significantly associated with short-term mortality in patients with sepsis, potentially influenced by the severity of sepsis. Monitoring HMGB-1 levels on the third and seventh day after admission can better evaluate its potential as a prognostic marker for sepsis mortality.

HEART & LUNG (2021)

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Article Immunology

Heparin prevents caspase-11-dependent septic lethality independent of anticoagulant properties

Yiting Tang et al.

Summary: Heparin prevents immune responses and reduces mortality in sepsis independently of its anticoagulant properties. This previously unrecognized function of heparin reveals a link between innate immune responses and coagulation.

IMMUNITY (2021)

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Article Multidisciplinary Sciences

A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis

Shenbin Liu et al.

Summary: The study reveals that the specificity of sensory neurons is crucial for driving specific autonomic pathways and anti-inflammatory effects at specific acupoints.

NATURE (2021)

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Article Oncology

Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy

Pascale Hubert et al.

Summary: In this study, it was demonstrated that targeting extracellular HMGB1 can significantly remodel the tumor immune microenvironment for more effective cancer therapy. Inhibition of HMGB1 led to reductions in immunosuppressive cells, such as myeloid-derived suppressor cells and regulatory T lymphocytes, while also enhancing the activation of immune cells like dendritic cells. Additionally, blocking HMGB1 improved the efficacy of anti-PD-1 cancer immunotherapy, suggesting that extracellular HMGB1 blockade could enhance current cancer immunotherapies.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Cell Biology

HMGB1 orchestrates STING-mediated senescence via TRIM30α modulation in cancer cells

Je-Jung Lee et al.

Summary: The study revealed that HMGB1 orchestrates STING-STAT6-p21-mediated senescence by regulating TRIM30α as an alternative anticancer mechanism.

CELL DEATH DISCOVERY (2021)

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Article Immunology

The inhibitory receptor TIM-3 limits activation of the cGAS-STING pathway in intra-tumoral dendritic cells by suppressing extracellular DNA uptake

Alvaro de Mingo Pulido et al.

Summary: Blockade of the inhibitory receptor TIM-3 has shown efficacy in clinical trials of cancer immunotherapy, specifically in enhancing antitumor immunity in mammary carcinomas by increasing CXCL9 expression by cDC1 cells. This increased expression required type I interferons and extracellular DNA, with DNA uptake and efficacy of TIM-3 blockade being dependent on HMGB1 and galectin-9-induced cell surface clustering of TIM-3, suggesting a potential mechanism for TIM-3 immunotherapy.

IMMUNITY (2021)

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Article Oncology

HMGB1 Promotes Resistance to Doxorubicin in Human Hepatocellular Carcinoma Cells by Inducing Autophagy via the AMPK/mTOR Signaling Pathway

Junhua Li et al.

Summary: The study revealed that HMGB1 enhances autophagy through the AMPK/mTOR pathway, promoting acquired drug resistance in HCC cells treated with doxorubicin (DOX). Inhibition of HMGB1 and autophagy increased sensitivity to DOX, suggesting HMGB1 inhibitors could be a promising targeted treatment strategy for HCC.

FRONTIERS IN ONCOLOGY (2021)

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Article Immunology

Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus

Johannes Hartl et al.

Summary: The majority of sporadic SLE patients with nephritis have reduced DNASE1L3 activity and neutralizing autoantibodies to DNASE1L3, leading to the accumulation of cfDNA in microparticles and increased disease severity. Autoantibody-mediated impairment of DNASE1L3 activity is a common non-genetic mechanism facilitating anti-dsDNA autoreactivity in patients with severe sporadic SLE.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Biochemistry & Molecular Biology

Circulating Nucleosomes as Potential Markers to Monitor COVID-19 Disease Progression

Etienne Cavalier et al.

Summary: The study found elevated levels of nucleosomes in the plasma of COVID-19 patients, especially in those with severe disease. Increased citrullinated nucleosomes levels indicate neutrophil activation in severely affected individuals. Furthermore, nucleosome levels correlate with disease severity and may serve as a guiding biomarker for treatment.

FRONTIERS IN MOLECULAR BIOSCIENCES (2021)

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Article Genetics & Heredity

Heterozygous HMGB1 loss-of-function variants are associated with developmental delay and microcephaly

Kevin Uguen et al.

Summary: 13q12.3 microdeletion syndrome is a rare cause of syndromic intellectual disability, and this study reports six patients with loss-of-function variants involving HMGB1, suggesting that haploinsufficiency of the HMGB1 gene may play a critical role in the pathogenesis of the syndrome.

CLINICAL GENETICS (2021)

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Article Immunology

HMGB1 promotes CXCL12-dependent egress of murine B cells from Peyer's patches in homeostasis

Lorenzo Spagnuolo et al.

Summary: The HMGB1-CXCL12 complex plays a crucial role in homeostasis by controlling B lymphocyte migration in the Peyer's patches. Inhibition of the complex results in reduced IgA production in the gut, indicating a novel target for controlling lymphocyte migration in mucosal immunity.

EUROPEAN JOURNAL OF IMMUNOLOGY (2021)

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Article Biochemistry & Molecular Biology

Dynamic Autoinhibition of the HMGB1 Protein via Electrostatic Fuzzy Interactions of Intrinsically Disordered Regions

Xi Wang et al.

Summary: This study investigates how D/E repeats cause autoinhibition of HMGB1 and its specific binding to cisplatin-modified DNA. By varying ionic strength, the conformational equilibrium between autoinhibited and uninhibited states can be shifted, revealing fuzzy interactions of D/E repeats with other intrinsically disordered regions. Mutations mimicking post-translational modifications relevant to nuclear export of HMGB1 can moderately modulate DNA-binding affinity, possibly by impacting the autoinhibition.

JOURNAL OF MOLECULAR BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence

Konstantinos Sofiadis et al.

Summary: The study reveals that HMGB1 plays a crucial role in coordinating chromatin folding and RNA homeostasis, acting as a regulatory loop controlling cell-autonomous and paracrine senescence. Additionally, HMGB1 is identified as a RNA-binding protein with rich interactions with RBPs involved in senescence regulation.

MOLECULAR SYSTEMS BIOLOGY (2021)

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Article Multidisciplinary Sciences

HMGB1 released from nociceptors mediates inflammation

Huan Yang et al.

Summary: Inflammation is initiated by molecular signatures of microbes and tissue injury, triggering the body's defensive response. Neuronal synthesis of HMGB1 is an important mediator of inflammation, with the release of HMGB1 by nociceptors playing a role in neurogenic inflammation.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Cell Biology

Rebalancing expression of HMGB1 redox isoforms to counteract muscular dystrophy

Giorgia Careccia et al.

Summary: This study identified the important role of high-mobility group box 1 (HMGB1) in muscular dystrophies (MDs), where HMGB1 oxidation is a detrimental process. Treatment with a non-oxidizable variant of HMGB1 improves the phenotype of MDs.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Cell Biology

Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer's disease and frontotemporal dementia

Sagar Gaikwad et al.

Summary: The study demonstrates that TauO-induced neuroinflammation is primarily mediated through HMGB1 release and inflammatory SASP, leading to astrocyte senescence. Inhibition of HMGB1 release can prevent TauO-induced cellular senescence, reduce neuroinflammation, and improve cognitive function.

CELL REPORTS (2021)

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Article Medicine, Research & Experimental

The extracellular innate-immune effector HMGB1 limits pathogenic bacterial biofilm proliferation

Aishwarya Devaraj et al.

Summary: This study reveals an extracellular function of HMGB1 in bacterial biofilm proliferation, disrupting biofilms while inducing an inflammatory response that can be attenuated by a single engineered amino acid change. The findings propose a model where extracellular HMGB1 balances inflammation and biofilm containment without excessive release of biofilm-resident bacteria.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Biochemistry & Molecular Biology

Uterine deficiency of high-mobility group box-1 (HMGB1) protein causes implantation defects and adverse pregnancy outcomes

Shizu Aikawa et al.

CELL DEATH AND DIFFERENTIATION (2020)

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Article Orthopedics

Early stage blockade of the alarmin HMGB1 reduces cartilage destruction in experimental OA

C. Aulin et al.

OSTEOARTHRITIS AND CARTILAGE (2020)

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Article Oncology

Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells

Jose Ignacio Gonzalez Solari et al.

BMC CANCER (2020)

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Article Biochemistry & Molecular Biology

RIPK3 collaborates with GSDMD to drive tissue injury in lethal polymicrobial sepsis

Hui Chen et al.

CELL DEATH AND DIFFERENTIATION (2020)

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Article Microbiology

TMEM173 Drives Lethal Coagulation in Sepsis

Hui Zhang et al.

CELL HOST & MICROBE (2020)

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Article Cell Biology

Identification of tetranectin-targeting monoclonal antibodies to treat potentially lethal sepsis

Weiqiang Chen et al.

SCIENCE TRANSLATIONAL MEDICINE (2020)

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Article Cell Biology

FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome

Fuming Li et al.

NATURE CELL BIOLOGY (2020)

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Editorial Material Immunology

Elevated serum levels of S100A8/A9 and HMGB1 at hospital admission are correlated with inferior clinical outcomes in COVID-19 patients

Liting Chen et al.

CELLULAR & MOLECULAR IMMUNOLOGY (2020)

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Article Cell Biology

Vitamin D attenuates HMGB1-mediated neointimal hyperplasia after percutaneous coronary intervention in swine

Mohan Satish et al.

MOLECULAR AND CELLULAR BIOCHEMISTRY (2020)

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Article Biochemistry & Molecular Biology

The α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuates hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation

Ravikumar A. Sitapara et al.

MOLECULAR MEDICINE (2020)

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Article Multidisciplinary Sciences

Hepatocellular carcinoma-derived high mobility group box 1 triggers M2 macrophage polarization via a TLR2/NOX2/autophagy axis

Dong-Jer Shiau et al.

SCIENTIFIC REPORTS (2020)

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Article Multidisciplinary Sciences

Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy

Jiaming Xue et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Multidisciplinary Sciences

Indirect regulation of HMGB1 release by gasdermin D

Allen Volchuk et al.

NATURE COMMUNICATIONS (2020)

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Article Immunology

HMGB1 Promotes Myeloid Egress and Limits Lymphatic Clearance of Malignant Pleural Effusions

Adam C. Soloff et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Microbiology

Extracellular SQSTM1 mediates bacterial septic death in mice through insulin receptor signalling

Borong Zhou et al.

NATURE MICROBIOLOGY (2020)

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Article Multidisciplinary Sciences

Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway

Enyong Dai et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

HMGB1 as a potential biomarker and therapeutic target for severe COVID-19

Ruochan Chen et al.

HELIYON (2020)

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Article Cell Biology

Intestinal epithelial HMGB1 inhibits bacterial infection via STAT3 regulation of autophagy

Yong-Guo Zhang et al.

AUTOPHAGY (2019)

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Article Biochemistry & Molecular Biology

The release and activity of HMGB1 in ferroptosis

Qirong Wen et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2019)

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Review Pharmacology & Pharmacy

Anti-HMGB1 monoclonal antibody therapy for a wide range of CNS and PNS diseases

Masahiro Nishibori et al.

JOURNAL OF PHARMACOLOGICAL SCIENCES (2019)

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Article Medicine, Research & Experimental

cGAS/STING axis mediates a topoisomerase II inhibitor induced tumor immunogenicity

Zining Wang et al.

JOURNAL OF CLINICAL INVESTIGATION (2019)

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Editorial Material Multidisciplinary Sciences

A peaceful death orchestrates immune balance in a chaotic environment

Adam C. Soloff et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Immunology

Ethyl Pyruvate Stimulates Regulatory T Cells and Ameliorates Type 1 Diabetes Development in Mice

Ivan Koprivica et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Article Oncology

Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine

Victoria D. Turubanova et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2019)

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Article Medicine, General & Internal

Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis

Serdar Turkyilmaz et al.

ARCHIVES OF MEDICAL SCIENCE (2019)

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Article Immunology

High mobility group box 1 orchestrates tissue regeneration via CXCR4

Mario Tirone et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2018)

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Article Microbiology

Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis

Rui Kang et al.

CELL HOST & MICROBE (2018)

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Article Gastroenterology & Hepatology

High mobility group protein B1 controls liver cancer initiation through yes-associated protein -dependent aerobic glycolysis

Ruochan Chen et al.

HEPATOLOGY (2018)

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Article Medicine, Research & Experimental

HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis (Publication with Expression of Concern. See vol. 129, pg. 1803, 2019)

Celine Hernandez et al.

JOURNAL OF CLINICAL INVESTIGATION (2018)

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Article Biochemistry & Molecular Biology

Exploring the biological functional mechanism of the HMGB1/TLR4/MD-2 complex by surface plasmon resonance

Mingzhu He et al.

MOLECULAR MEDICINE (2018)

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Article Cell Biology

PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of Mitochondrial Iron-Mediated Immunometabolism

Changfeng Li et al.

DEVELOPMENTAL CELL (2018)

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Article Cell Biology

Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis

Norma Maugeri et al.

SCIENCE TRANSLATIONAL MEDICINE (2018)

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Article Immunology

The Endotoxin Delivery Protein HMGB1 Mediates Caspase-11-Dependent Lethality in Sepsis

Meihong Deng et al.

IMMUNITY (2018)

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Article Multidisciplinary Sciences

Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death

Pontus Orning et al.

SCIENCE (2018)

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Article Oncology

Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1(+) regulatory B cell expansion

Linsen Ye et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2018)

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Article Hematology

Platelet HMGB1 is required for efficient bacterial clearance in intra-abdominal bacterial sepsis in mice

Hui Zhou et al.

BLOOD ADVANCES (2018)

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Article Hematology

The platelet NLRP3 inflammasome is upregulated in sickle cell disease via HMGB1/TLR4 and Bruton tyrosine kinase

Sebastian Vogel et al.

BLOOD ADVANCES (2018)

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Article Biochemistry & Molecular Biology

Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity

Takahiro Horiuchi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2017)

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Article Multidisciplinary Sciences

cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein-DNA ladders

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Hepatitis B virus X protein stimulates high mobility group box 1 secretion and enhances hepatocellular carcinoma metastasis

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Critical role of RAGE and HMGB1 in inflammatory heart disease

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HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism

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AUTOPHAGY (2016)

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C1q and HMGB1 reciprocally regulate human macrophage polarization

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High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy

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Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice

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A core viral protein binds host nucleosomes to sequester immune danger signals

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PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation

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Modulation of Macrophage Polarization and HMGB1-TLR2/TLR4 Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice

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HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer's disease

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Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes (Publication with Expression of Concern. See vol. 3, 2018)

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Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation

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MD-2 is required for disulfide HMGB1-dependent TLR4 signaling

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HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi

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HMGB1 Enhances Immune Suppression by Facilitating the Differentiation and Suppressive Activity of Myeloid-Derived Suppressor Cells

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Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis

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High-Mobility Group Box 1 Is Dispensable for Autophagy, Mitochondrial Quality Control, and Organ Function In Vivo

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Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release and Limits Acute Pancreatitis in Mice

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Hepatocyte-Specific High-Mobility Group Box 1 Deletion Worsens the Injury in Liver Ischemia/Reperfusion: A Role for Intracellular High-Mobility Group Box 1 in Cellular Protection

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Distinct Dendritic Cell Subsets Dictate the Fate Decision between Effector and Memory CD8+ T Cell Differentiation by a CD24-Dependent Mechanism

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Expression and Effects of High-Mobility Group Box 1 in Cervical Cancer

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PARP-1 Mediates LPS-Induced HMGB1 Release by Macrophages through Regulation of HMGB1 Acetylation

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Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma

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Sequestering HMGB1 via DNA-Conjugated Beads Ameliorates Murine Colitis

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HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4

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Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis

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Poly IC Triggers a Cathepsin D- and IPS-1-Dependent Pathway to Enhance Cytokine Production and Mediate Dendritic Cell Necroptosis

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Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients

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p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes

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Conditional ablation of HMGB1 in mice reveals its protective function against endotoxemia and bacterial infection

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

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Tanshinone IIA sodium sulfonate facilitates endocytic HMGB1 uptake

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Inhibitory effects of lycopene on HMGB1-mediated pro-inflammatory responses in both cellular and animal models

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Circulating nucleosomes as a predictor of sepsis and organ dysfunction in critically ill patients

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HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4

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Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release

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Novel role of PKR in inflammasome activation and HMGB1 release

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Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1

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Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis

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Atorvastatin reduces serum HMGB1 levels in patients with hyperlipidemia

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Diagnostic Accuracy of HMGB-1, s-TREM-1, and CD64 as Markers of Sepsis in Patients Recently Admitted to the Emergency Department

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EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages

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Redox State-Dependent Interaction of HMGB1 and Cisplatin-Modified DNA

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Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock

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Heparin changes the conformation of high-mobility group protein 1 and decreases its affinity toward receptor for advanced glycation endproducts in vitro

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HMGB1 Acts on Microglia Mac1 to Mediate Chronic Neuroinflammation That Drives Progressive Neurodegeneration

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DNA-based strategies for blocking HMGB1 cytokine activity: design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes

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Monoclonal Anti-HMGB1 (High Mobility Group Box Chromosomal Protein 1) Antibody Protection in Two Experimental Arthritis Models

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HMGB1 inhibitor glycyrrhizin attenuates intracerebral hemorrhage-induced injury in rats

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Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-mobility group box proteins (HMGBs)

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Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit

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Protective Targeting of High Mobility Group Box Chromosomal Protein 1 in a Spontaneous Arthritis Model

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Endogenous HMGB1 regulates autophagy

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Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia

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JOURNAL OF IMMUNOLOGY (2010)

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HMGB1 release and redox regulates autophagy and apoptosis in cancer cells

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A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release

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Quercetin Prevents LPS-Induced High-Mobility Group Box 1 Release and Proinflammatory Function

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Early endosomes and endosomal coatomer are required for autophagy

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JOURNAL OF CELL BIOLOGY (2009)

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HMGB1 Is Phosphorylated by Classical Protein Kinase C and Is Secreted by a Calcium-Dependent Mechanism

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Low-dose cisplatin administration in murine cecal ligation and puncture prevents the systemic release of HMGB1 and attenuates lethality

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Chromatin-Specific Remodeling by HMGB1 and Linker Histone H1 Silences Proinflammatory Genes during Endotoxin Tolerance

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HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses

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CD24 and Siglec-10 Selectively Repress Tissue Damage-Induced Immune Responses

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Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2008)

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Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein

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IMMUNITY (2008)

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Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE

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JOURNAL OF EXPERIMENTAL MEDICINE (2008)

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Oxaliplatin retains HMGB1 intranuclearly and ameliorates collagen type II-induced arthritis

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ARTHRITIS RESEARCH & THERAPY (2008)

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HMGB1 release induced by liver ischemia involves Toll-like receptor 4-dependent reactive oxygen species production and calcium-mediated signaling

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A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA

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Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy

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Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE

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Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities

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CHEMISTRY & BIOLOGY (2007)

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Article Critical Care Medicine

Selective α7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis

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CRITICAL CARE MEDICINE (2007)

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A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinfiammatory mediator, high mobility group box 1

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Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1

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A comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: A prospective study

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Pivotal advance: Analysis of proinflammatory activity of highly purified eukaryotic recombinant HMGB1 (amphoterin)

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JOURNAL OF LEUKOCYTE BIOLOGY (2007)

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Article Critical Care Medicine

Circulating high-mobility group box 1 (HMGB1) concentrations are elevated in both uncomplicated pneumonia and pneumonia with severe sepsis

Derek C. Angus et al.

CRITICAL CARE MEDICINE (2007)

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The extracellular release of HMGB1 during apoptotic cell death

Charles W. Bell et al.

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The aqueous extract of a popular herbal nutrient supplement, Angelica sinensis, protects mice against lethal endotoxemia and sepsis

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The effects of CpG DNA on HMGB1 release by murine macrophage cell lines

WW Jiang et al.

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Reconstitution of 5′-directed human mismatch repair in a purified system

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The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion

A Tsung et al.

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Ethyl pyruvate ameliorates liver ischemia-reperfusion injury by decreasing hepatic necrosis and apoptosis

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TRANSPLANTATION (2005)

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Reversing established sepsis with antagonists of endogenous high-mobility group box 1

H Yang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2004)

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Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion

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EMBO JOURNAL (2003)

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High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine

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ARTHRITIS AND RHEUMATISM (2003)

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IFN-γ induces high mobility group box 1 protein release partly through a TNF-dependent mechanism

B Rendon-Mitchell et al.

JOURNAL OF IMMUNOLOGY (2003)

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Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation

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The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway

S Gardella et al.

EMBO REPORTS (2002)

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Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2002)

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Release of chromatin protein HMGB1 by necrotic cells triggers inflammation

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High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes

U Andersson et al.

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Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases

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