The multifunctional protein HMGB1: 50 years of discovery.
Journal
Nature reviews. Immunology
ISSN: 1474-1741
Titre abrégé: Nat Rev Immunol
Pays: England
ID NLM: 101124169
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
accepted:
16
05
2023
medline:
27
11
2023
pubmed:
16
6
2023
entrez:
15
6
2023
Statut:
ppublish
Résumé
Fifty years since the initial discovery of HMGB1 in 1973 as a structural protein of chromatin, HMGB1 is now known to regulate diverse biological processes depending on its subcellular or extracellular localization. These functions include promoting DNA damage repair in the nucleus, sensing nucleic acids and inducing innate immune responses and autophagy in the cytosol and binding protein partners in the extracellular environment and stimulating immunoreceptors. In addition, HMGB1 is a broad sensor of cellular stress that balances cell death and survival responses essential for cellular homeostasis and tissue maintenance. HMGB1 is also an important mediator secreted by immune cells that is involved in a range of pathological conditions, including infectious diseases, ischaemia-reperfusion injury, autoimmunity, cardiovascular and neurodegenerative diseases, metabolic disorders and cancer. In this Review, we discuss the signalling mechanisms, cellular functions and clinical relevance of HMGB1 and describe strategies to modify its release and biological activities in the setting of various diseases.
Identifiants
pubmed: 37322174
doi: 10.1038/s41577-023-00894-6
pii: 10.1038/s41577-023-00894-6
doi:
Substances chimiques
HMGB1 Protein
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
824-841Informations de copyright
© 2023. Springer Nature Limited.
Références
Goodwin, G. H. & Johns, E. W. Isolation and characterisation of two calf-thymus chromatin non-histone proteins with high contents of acidic and basic amino acids. Eur. J. Biochem. 40, 215–219 (1973).
pubmed: 4772679
Sharman, A. C., Hay-Schmidt, A. & Holland, P. W. Cloning and analysis of an HMG gene from the lamprey Lampetra fluviatilis: gene duplication in vertebrate evolution. Gene 184, 99–105 (1997).
pubmed: 9016958
Calogero, S. et al. The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nat. Genet. 22, 276–280 (1999).
pubmed: 10391216
Aikawa, S. et al. Uterine deficiency of high-mobility group box-1 (HMGB1) protein causes implantation defects and adverse pregnancy outcomes. Cell Death Differ. 27, 1489–1504 (2020).
pubmed: 31595043
Yanai, H. et al. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature 462, 99–103 (2009). This study reports that cytosolic HMGB1 is a mediator of nucleic-acid-induced immune responses.
pubmed: 19890330
Tang, D. et al. Endogenous HMGB1 regulates autophagy. J. Cell Biol. 190, 881–892 (2010). This study reports that cytosolic HMGB1 is a mediator of autophagy.
pubmed: 20819940
pmcid: 2935581
Tsung, A. et al. The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia–reperfusion. J. Exp. Med. 201, 1135–1143 (2005). This study reports that HMGB1 is a mediator of sterile inflammation.
pubmed: 15795240
pmcid: 2213120
Ling, Y. et al. Heparin changes the conformation of high-mobility group protein 1 and decreases its affinity toward receptor for advanced glycation endproducts in vitro. Int. Immunopharmacol. 11, 187–193 (2011).
pubmed: 21095260
Liu, R. et al. Establishment of in vitro binding assay of high mobility group box-1 and S100A12 to receptor for advanced glycation endproducts: heparin’s effect on binding. Acta Med. Okayama 63, 203–211 (2009).
pubmed: 19727205
He, M., Bianchi, M. E., Coleman, T. R., Tracey, K. J. & Al-Abed, Y. Exploring the biological functional mechanism of the HMGB1/TLR4/MD-2 complex by surface plasmon resonance. Mol. Med. 24, 21 (2018).
pubmed: 30134799
pmcid: 6085627
Yang, H. et al. A critical cysteine is required for HMGB1 binding to toll-like receptor 4 and activation of macrophage cytokine release. Proc. Natl Acad. Sci. USA 107, 11942–11947 (2010).
pubmed: 20547845
pmcid: 2900689
Huang, J. et al. DAMPs, ageing, and cancer: the ‘DAMP hypothesis’. Ageing Res. Rev. 24, 3–16 (2015).
pubmed: 25446804
Kleinschmidt, J. A., Seiter, A. & Zentgraf, H. Nucleosome assembly in vitro: separate histone transfer and synergistic interaction of native histone complexes purified from nuclei of Xenopus laevis oocytes. EMBO J. 9, 1309–1318 (1990).
pubmed: 2323341
pmcid: 551809
Bianchi, M. E., Beltrame, M. & Paonessa, G. Specific recognition of cruciform DNA by nuclear protein HMG1. Science 243, 1056–1059 (1989).
pubmed: 2922595
Pil, P. M. & Lippard, S. J. Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin. Science 256, 234–237 (1992).
pubmed: 1566071
Ru, H. et al. Molecular mechanism of V(D)J recombination from synaptic RAG1–RAG2 complex structures. Cell 163, 1138–1152 (2015).
pubmed: 26548953
pmcid: 4690471
Zhang, Y. et al. Reconstitution of 5′-directed human mismatch repair in a purified system. Cell 122, 693–705 (2005).
pubmed: 16143102
Wang, X. et al. Dynamic autoinhibition of the HMGB1 protein via electrostatic fuzzy interactions of intrinsically disordered regions. J. Mol. Biol. 433, 167122 (2021).
pubmed: 34181980
pmcid: 8380713
Mensah, M. A. et al. Aberrant phase separation and nucleolar dysfunction in rare genetic diseases. Nature 614, 564–571 (2023).
pubmed: 36755093
pmcid: 9931588
Uguen, K. et al. Heterozygous HMGB1 loss-of-function variants are associated with developmental delay and microcephaly. Clin. Genet. 100, 386–395 (2021).
pubmed: 34164801
Venereau, E. et al. Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release. J. Exp. Med. 209, 1519–1528 (2012).
pubmed: 22869893
pmcid: 3428943
Park, S. & Lippard, S. J. Redox state-dependent interaction of HMGB1 and cisplatin-modified DNA. Biochemistry 50, 2567–2574 (2011).
pubmed: 21355578
El Gazzar, M. et al. Chromatin-specific remodeling by HMGB1 and linker histone H1 silences proinflammatory genes during endotoxin tolerance. Mol. Cell. Biol. 29, 1959–1971 (2009).
pubmed: 19158276
Huang, H. et al. Hepatocyte specific HMGB1 deletion worsens the injury in liver ischemia/reperfusion: a role for intracellular HMGB1 in cellular protection. Hepatology 59, 1984–1997 (2014).
pubmed: 24375466
Kang, R. et al. Intracellular Hmgb1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice. Gastroenterology 146, 1097–1107 (2014).
pubmed: 24361123
Chen, Q. et al. Circulating nucleosomes as a predictor of sepsis and organ dysfunction in critically ill patients. Int. J. Infect. Dis. 16, e558–e564 (2012).
pubmed: 22609014
Cavalier, E. et al. Circulating nucleosomes as potential markers to monitor COVID-19 disease progression. Front. Mol. Biosci. 8, 600881 (2021).
pubmed: 33816549
pmcid: 8012533
Wang, H. et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248–251 (1999). This study reports that HMGB1 can be secreted into the extracellular space to mediate inflammation.
pubmed: 10398600
Gardella, S. et al. The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep. 3, 995–1001 (2002). This study reports the mechanism of HMGB1 secretion.
pubmed: 12231511
pmcid: 1307617
Rendon-Mitchell, B. et al. IFN-gamma induces high mobility group box 1 protein release partly through a TNF-dependent mechanism. J. Immunol. 170, 3890–3897 (2003).
pubmed: 12646658
Deng, M. et al. The endotoxin delivery protein HMGB1 mediates caspase-11-dependent lethality in sepsis. Immunity 49, 740–753.e7 (2018).
pubmed: 30314759
pmcid: 6300139
Yang, H. et al. HMGB1 released from nociceptors mediates inflammation. Proc. Natl Acad. Sci. USA 118, e2102034118 (2021).
pubmed: 34385304
pmcid: 8379951
Scaffidi, P., Misteli, T. & Bianchi, M. E. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418, 191–195 (2002). This study reports that HMGB1 functions as a DAMP during necrosis.
pubmed: 12110890
Kang, R. et al. HMGB1 in health and disease. Mol. Asp. Med. 40, 1–116 (2014).
Urbonaviciute, V. et al. Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J. Exp. Med. 205, 3007–3018 (2008).
pubmed: 19064698
pmcid: 2605236
Ivanov, S. et al. A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood 110, 1970–1981 (2007).
pubmed: 17548579
pmcid: 1976374
Tian, J. et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat. Immunol. 8, 487–496 (2007).
pubmed: 17417641
Rouhiainen, A., Tumova, S., Valmu, L., Kalkkinen, N. & Rauvala, H. Pivotal advance: analysis of proinflammatory activity of highly purified eukaryotic recombinant HMGB1 (amphoterin). J. Leukoc. Biol. 81, 49–58 (2007).
pubmed: 16980512
Iachettini, S. et al. The telomeric protein TERF2/TRF2 impairs HMGB1-driven autophagy. Autophagy https://doi.org/10.1080/15548627.2022.2138687 (2022).
doi: 10.1080/15548627.2022.2138687
pubmed: 36310382
pmcid: 10240986
Livesey, K. M. et al. p53/HMGB1 complexes regulate autophagy and apoptosis. Cancer Res. 72, 1996–2005 (2012).
pubmed: 22345153
pmcid: 3417120
Kim, S. W., Oh, S. A., Seol, S. I., Davaanyam, D. & Lee, J. K. Cytosolic HMGB1 mediates LPS-induced autophagy in microglia by interacting with NOD2 and suppresses its proinflammatory function. Cells 11, 2410 (2022).
pubmed: 35954253
pmcid: 9368039
Huebener, P. et al. High-mobility group box 1 is dispensable for autophagy, mitochondrial quality control, and organ function in vivo. Cell Metab. 19, 539–547 (2014).
pubmed: 24606906
pmcid: 4099361
Deretic, V., Saitoh, T. & Akira, S. Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 13, 722–737 (2013).
pubmed: 24064518
pmcid: 5340150
Wen, Q., Liu, J., Kang, R., Zhou, B. & Tang, D. The release and activity of HMGB1 in ferroptosis. Biochem. Biophys. Res. Commun. 510, 278–283 (2019).
pubmed: 30686534
Dupont, N. et al. Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1beta. EMBO J. 30, 4701–4711 (2011).
pubmed: 22068051
pmcid: 3243609
Wang, Z. et al. Autophagy-based unconventional secretion of HMGB1 by keratinocytes plays a pivotal role in psoriatic skin inflammation. Autophagy 17, 529–552 (2021).
pubmed: 32019420
Kim, Y. H. et al. Secretory autophagy machinery and vesicular trafficking are involved in HMGB1 secretion. Autophagy 17, 2345–2362 (2021).
pubmed: 33017561
Zhou, B. et al. Extracellular SQSTM1 mediates bacterial septic death in mice through insulin receptor signalling. Nat. Microbiol. 5, 1576–1587 (2020).
pubmed: 33077977
pmcid: 7977680
Zhu, X. et al. Cytosolic HMGB1 controls the cellular autophagy/apoptosis checkpoint during inflammation. J. Clin. Invest. 125, 1098–1110 (2015).
pubmed: 25642769
pmcid: 4362239
Zeng, X., Liu, F., Liu, K., Xin, J. & Chen, J. HMGB1 could restrict 1,3-beta-glucan induced mice lung inflammation by affecting beclin1 and Bcl2 interaction and promoting the autophagy of epithelial cells. Ecotoxicol. Environ. Saf. 222, 112460 (2021).
pubmed: 34243113
Zhang, Y. G. et al. Intestinal epithelial HMGB1 inhibits bacterial infection via STAT3 regulation of autophagy. Autophagy 15, 1935–1953 (2019).
pubmed: 30894054
pmcid: 6844505
Yanai, H. et al. Conditional ablation of HMGB1 in mice reveals its protective function against endotoxemia and bacterial infection. Proc. Natl Acad. Sci. USA 110, 20699–20704 (2013).
pubmed: 24302768
pmcid: 3870753
Parker, K. H., Horn, L. A. & Ostrand-Rosenberg, S. High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy. J. Leukoc. Biol. 100, 463–470 (2016).
pubmed: 26864266
pmcid: 4982609
Xue, J. et al. Asbestos induces mesothelial cell transformation via HMGB1-driven autophagy. Proc. Natl Acad. Sci. USA 117, 25543–25552 (2020).
pubmed: 32999071
pmcid: 7568322
Li, J. et al. HMGB1 promotes resistance to doxorubicin in human hepatocellular carcinoma cells by inducing autophagy via the AMPK/mTOR signaling pathway. Front. Oncol. 11, 739145 (2021).
pubmed: 34778055
pmcid: 8578906
Tang, D. et al. HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene 29, 5299–5310 (2010).
pubmed: 20622903
pmcid: 2945431
Kazama, H. et al. Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein. Immunity 29, 21–32 (2008).
pubmed: 18631454
pmcid: 2704496
Andreeva, L. et al. cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein–DNA ladders. Nature 549, 394–398 (2017).
pubmed: 28902841
Razi, M., Chan, E. Y. & Tooze, S. A. Early endosomes and endosomal coatomer are required for autophagy. J. Cell Biol. 185, 305–321 (2009).
pubmed: 19364919
pmcid: 2700373
Merenmies, J., Pihlaskari, R., Laitinen, J., Wartiovaara, J. & Rauvala, H. 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane. J. Biol. Chem. 266, 16722–16729 (1991).
pubmed: 1885601
Tadie, J. M. et al. HMGB1 promotes neutrophil extracellular trap formation through interactions with toll-like receptor 4. Am. J. Physiol. Lung Cell Mol. Physiol. 304, L342–L349 (2013).
pubmed: 23316068
pmcid: 3602738
Ahrens, I. et al. HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi. Thromb. Haemost. 114, 994–1003 (2015).
pubmed: 26202300
Zhan, Y. et al. HMGB1-mediated neutrophil extracellular trap formation exacerbates intestinal ischemia/reperfusion-induced acute lung injury. J. Immunol. 208, 968–978 (2022).
pubmed: 35063996
Zhang, X. L. et al. HMGB1-promoted neutrophil extracellular traps contribute to cardiac diastolic dysfunction in mice. J. Am. Heart Assoc. 11, e023800 (2022).
pubmed: 35156391
pmcid: 9245819
Maugeri, N. et al. Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis. Sci. Transl. Med. 10, eaao3089 (2018).
pubmed: 30045975
Vogel, S. et al. Platelet-derived HMGB1 is a critical mediator of thrombosis. J. Clin. Invest. 125, 4638–4654 (2015).
pubmed: 26551681
pmcid: 4665785
Jiang, W., Li, J., Gallowitsch-Puerta, M., Tracey, K. J. & Pisetsky, D. S. The effects of CpG DNA on HMGB1 release by murine macrophage cell lines. J. Leukoc. Biol. 78, 930–936 (2005).
pubmed: 16081598
Lamkanfi, M. et al. Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia. J. Immunol. 185, 4385–4392 (2010).
pubmed: 20802146
Andersson, U. et al. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes. J. Exp. Med. 192, 565–570 (2000). This study reports that HMGB1 can induce cytokine production.
pubmed: 10952726
pmcid: 2193240
Schiraldi, M. et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J. Exp. Med. 209, 551–563 (2012). This study reports that the activity of HMGB1 is regulated by its redox status.
pubmed: 22370717
pmcid: 3302219
Hartl, J. et al. Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus. J. Exp. Med. 218, e20201138 (2021).
pubmed: 33783474
pmcid: 8020718
Spagnuolo, L. et al. HMGB1 promotes CXCL12-dependent egress of murine B cells from Peyer’s patches in homeostasis. Eur. J. Immunol. 51, 1980–1991 (2021).
pubmed: 34060652
pmcid: 8453951
Xu, J. et al. Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis. Cell Death Differ. 21, 1229–1239 (2014).
pubmed: 24769733
pmcid: 4085529
Chen, W. et al. Identification of tetranectin-targeting monoclonal antibodies to treat potentially lethal sepsis. Sci. Transl. Med. 12, eaaz3833 (2020).
pubmed: 32295901
pmcid: 7169984
Hernandez-Pando, R. et al. The role of high mobility group box 1 protein (HMGB1) in the immunopathology of experimental pulmonary tuberculosis. PLoS ONE 10, e0133200 (2015).
pubmed: 26201072
pmcid: 4511675
Yang, H. et al. Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc. Natl Acad. Sci. USA 101, 296–301 (2004).
pubmed: 14695889
Yang, M. et al. Chloroquine inhibits HMGB1 inflammatory signaling and protects mice from lethal sepsis. Biochem. Pharmacol. 86, 410–418 (2013).
pubmed: 23707973
pmcid: 3713089
Devaraj, A. et al. The extracellular innate-immune effector HMGB1 limits pathogenic bacterial biofilm proliferation. J. Clin. Invest. 131, e140527 (2021).
pubmed: 34396989
pmcid: 8363290
Zhou, H. et al. Platelet HMGB1 is required for efficient bacterial clearance in intra-abdominal bacterial sepsis in mice. Blood Adv. 2, 638–648 (2018).
pubmed: 29563120
pmcid: 5873229
Tsung, A. et al. HMGB1 release induced by liver ischemia involves toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J. Exp. Med. 204, 2913–2923 (2007).
pubmed: 17984303
pmcid: 2118528
Yang, H. et al. MD-2 is required for disulfide HMGB1-dependent TLR4 signaling. J. Exp. Med. 212, 5–14 (2015).
pubmed: 25559892
pmcid: 4291531
Taguchi, A. et al. Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405, 354–360 (2000). This study reports the oncogenic role of HMGB1.
pubmed: 10830965
Wang, J. et al. HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-kappaB signaling pathways. Int. J. Mol. Med. 45, 61–80 (2020).
pubmed: 31746367
Chen, G. Y., Tang, J., Zheng, P. & Liu, Y. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323, 1722–1725 (2009).
pubmed: 19264983
pmcid: 2765686
Chiba, S. et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat. Immunol. 13, 832–842 (2012).
pubmed: 22842346
pmcid: 3622453
de Mingo Pulido, A. et al. The inhibitory receptor TIM-3 limits activation of the cGAS–STING pathway in intra-tumoral dendritic cells by suppressing extracellular DNA uptake. Immunity 54, 1154–1167.e7 (2021).
pubmed: 33979578
pmcid: 8192496
Kim, T. S., Gorski, S. A., Hahn, S., Murphy, K. M. & Braciale, T. J. Distinct dendritic cell subsets dictate the fate decision between effector and memory CD8(+) T cell differentiation by a CD24-dependent mechanism. Immunity 40, 400–413 (2014).
pubmed: 24631155
pmcid: 4017923
Zhang, H. et al. TMEM173 drives lethal coagulation in sepsis. Cell Host Microbe 27, 556–570.e6 (2020).
pubmed: 32142632
pmcid: 7316085
Kang, R. et al. Lipid peroxidation drives gasdermin D-mediated pyroptosis in lethal polymicrobial sepsis. Cell Host. Microbe 24, 97–108.e4 (2018).
pubmed: 29937272
pmcid: 6043361
Yen, Y. C. et al. Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias. Sci. Adv. 8, eabn8063 (2022).
pubmed: 35857509
pmcid: 9278869
Tang, D. et al. Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1. J. Leukoc. Biol. 81, 741–747 (2007).
pubmed: 17135572
Tirone, M. et al. High mobility group box 1 orchestrates tissue regeneration via CXCR4. J. Exp. Med. 215, 303–318 (2018).
pubmed: 29203538
pmcid: 5748844
Bell, C. W., Jiang, W., Reich, C. F. III & Pisetsky, D. S. The extracellular release of HMGB1 during apoptotic cell death. Am. J. Physiol. Cell Physiol. 291, C1318–C1325 (2006).
pubmed: 16855214
Volchuk, A., Ye, A., Chi, L., Steinberg, B. E. & Goldenberg, N. M. Indirect regulation of HMGB1 release by gasdermin D. Nat. Commun. 11, 4561 (2020).
pubmed: 32917873
pmcid: 7486936
Lu, B. et al. Novel role of PKR in inflammasome activation and HMGB1 release. Nature 488, 670–674 (2012).
pubmed: 22801494
pmcid: 4163918
Kamiya, M. et al. Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies. Nat. Commun. 13, 166 (2022).
pubmed: 35013338
pmcid: 8748624
Zou, J. et al. Poly IC triggers a cathepsin D- and IPS-1-dependent pathway to enhance cytokine production and mediate dendritic cell necroptosis. Immunity 38, 717–728 (2013).
pubmed: 23601685
Kayagaki, N. et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature 591, 131–136 (2021).
pubmed: 33472215
Borges, J. P. et al. Glycine inhibits NINJ1 membrane clustering to suppress plasma membrane rupture in cell death. eLife 11, e78609 (2022).
pubmed: 36468682
pmcid: 9754625
Rogers, C. et al. Cleavage of DFNA5 by caspase-3 during apoptosis mediates progression to secondary necrotic/pyroptotic cell death. Nat. Commun. 8, 14128 (2017).
pubmed: 28045099
pmcid: 5216131
Taniguchi, N. et al. High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum. 48, 971–981 (2003).
pubmed: 12687539
Ostberg, T. et al. Protective targeting of high mobility group box chromosomal protein 1 in a spontaneous arthritis model. Arthritis Rheum. 62, 2963–2972 (2010).
pubmed: 20533288
Bangert, A. et al. Critical role of RAGE and HMGB1 in inflammatory heart disease. Proc. Natl Acad. Sci. USA 113, E155–E164 (2016).
pubmed: 26715748
Fu, L. et al. Therapeutic effects of anti-HMGB1 monoclonal antibody on pilocarpine-induced status epilepticus in mice. Sci. Rep. 7, 1179 (2017).
pubmed: 28446773
pmcid: 5430706
Fujita, K. et al. HMGB1, a pathogenic molecule that induces neurite degeneration via TLR4-MARCKS, is a potential therapeutic target for Alzheimer’s disease. Sci. Rep. 6, 31895 (2016).
pubmed: 27557632
pmcid: 4997258
Koprivica, I., Vujicic, M., Gajic, D., Saksida, T. & Stojanovic, I. Ethyl pyruvate stimulates regulatory T cells and ameliorates type 1 diabetes development in mice. Front. Immunol. 9, 3130 (2018).
pubmed: 30687329
Soloff, A. C. & Lotze, M. T. A peaceful death orchestrates immune balance in a chaotic environment. Proc. Natl Acad. Sci. USA 116, 22901–22903 (2019).
pubmed: 31653759
pmcid: 6859350
Mogilenko, D. A., Shchukina, I. & Artyomov, M. N. Immune ageing at single-cell resolution. Nat. Rev. Immunol. 22, 484–498 (2022).
pubmed: 34815556
Enokido, Y., Yoshitake, A., Ito, H. & Okazawa, H. Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain. Biochem. Biophys. Res. Commun. 376, 128–133 (2008).
pubmed: 18762169
Gao, H. M. et al. HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. J. Neurosci. 31, 1081–1092 (2011).
pubmed: 21248133
pmcid: 3046932
Karuppagounder, V. et al. Modulation of macrophage polarization and HMGB1-TLR2/TLR4 cascade plays a crucial role for cardiac remodeling in senescence-accelerated prone mice. PLoS ONE 11, e0152922 (2016).
pubmed: 27070323
pmcid: 4829159
Sofiadis, K. et al. HMGB1 coordinates SASP-related chromatin folding and RNA homeostasis on the path to senescence. Mol. Syst. Biol. 17, e9760 (2021).
pubmed: 34166567
pmcid: 8224457
Davalos, A. R. et al. p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J. Cell. Biol. 201, 613–629 (2013).
pubmed: 23649808
pmcid: 3653366
Li, F. et al. FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome. Nat. Cell Biol. 22, 728–739 (2020).
pubmed: 32367049
pmcid: 7286794
Gaikwad, S. et al. Tau oligomer induced HMGB1 release contributes to cellular senescence and neuropathology linked to Alzheimer’s disease and frontotemporal dementia. Cell Rep. 36, 109419 (2021).
pubmed: 34289368
pmcid: 8341760
Lee, J. J. et al. HMGB1 orchestrates STING-mediated senescence via TRIM30alpha modulation in cancer cells. Cell Death Discov. 7, 28 (2021).
pubmed: 33558529
pmcid: 7870821
Hernandez, C. et al. HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis. J. Clin. Invest. 128, 2436–2451 (2018).
pubmed: 29558367
pmcid: 5983315
Chen, R. et al. High mobility group protein B1 controls liver cancer initiation through yes-associated protein-dependent aerobic glycolysis. Hepatology 67, 1823–1841 (2018).
pubmed: 29149457
Kang, R. et al. Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer. Cell Res. 27, 916–932 (2017). This study reports the tumour suppressor role of HMGB1.
pubmed: 28374746
pmcid: 5518983
Bald, T. et al. Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature 507, 109–113 (2014).
pubmed: 24572365
Parker, K. H. et al. HMGB1 enhances immune suppression by facilitating the differentiation and suppressive activity of myeloid-derived suppressor cells. Cancer Res. 74, 5723–5733 (2014).
pubmed: 25164013
pmcid: 4199911
Hubert, P. et al. Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy. J. Immunother. Cancer 9, e001966 (2021).
pubmed: 33712445
pmcid: 7959241
Conche, C. et al. Combining ferroptosis induction with MDSC blockade renders primary tumours and metastases in liver sensitive to immune checkpoint blockade. Gut https://doi.org/10.1136/gutjnl-2022-327909 (2023).
doi: 10.1136/gutjnl-2022-327909
pubmed: 36707233
Dai, E. et al. Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway. Nat. Commun. 11, 6339 (2020).
pubmed: 33311482
pmcid: 7732843
Li, C. et al. PINK1 and PARK2 suppress pancreatic tumorigenesis through control of mitochondrial iron-mediated immunometabolism. Dev. Cell 46, 441–455 e448 (2018).
pubmed: 30100261
pmcid: 7654182
Gopal, A. et al. TIRAP drives myelosuppression through an Ifngamma-Hmgb1 axis that disrupts the endothelial niche in mice. J. Exp. Med. 219, e20200731 (2022).
pubmed: 35089323
pmcid: 8932532
Ye, L. et al. Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1(+) regulatory B cell expansion. J. Immunother. Cancer 6, 145 (2018).
pubmed: 30526680
pmcid: 6288912
Kam, N. W. et al. Peritumoral B cells drive proangiogenic responses in HMGB1-enriched esophageal squamous cell carcinoma. Angiogenesis 25, 181–203 (2022).
pubmed: 34617194
Liu, M. et al. The HMGB1 (C106A) mutation inhibits IL-10-producing CD19(hi)FcgammaRIIb(hi) B cell expansion by suppressing STAT3 activation in mice. Front. Immunol. 13, 975551 (2022).
pubmed: 35983056
pmcid: 9378787
Soloff, A. C. et al. HMGB1 promotes myeloid egress and limits lymphatic clearance of malignant pleural effusions. Front. Immunol. 11, 2027 (2020).
pubmed: 33013860
pmcid: 7498625
Rojas, A. et al. HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism. Tumour Biol. 37, 3321–3329 (2016).
pubmed: 26440051
Shiau, D. J. et al. Hepatocellular carcinoma-derived high mobility group box 1 triggers M2 macrophage polarization via a TLR2/NOX2/autophagy axis. Sci. Rep. 10, 13582 (2020).
pubmed: 32788720
pmcid: 7423894
Apetoh, L. et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13, 1050–1059 (2007). This study reports that HMGB1 is a mediator of immunogenic cell death.
pubmed: 17704786
Solari, J. I. G. et al. Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells. BMC Cancer 20, 474 (2020).
pubmed: 32456685
pmcid: 7251700
Fahmueller, Y. N. et al. Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients. Int. J. Cancer 132, 2349–2358 (2013).
pubmed: 23047645
Gdynia, G. et al. The HMGB1 protein induces a metabolic type of tumour cell death by blocking aerobic respiration. Nat. Commun. 7, 10764 (2016).
pubmed: 26948869
pmcid: 4786644
Li, Z. et al. Autophagy-based unconventional secretion of HMGB1 in glioblastoma promotes chemosensitivity to temozolomide through macrophage M1-like polarization. J. Exp. Clin. Cancer Res. 41, 74 (2022).
pubmed: 35193644
pmcid: 8862393
Wang, Z. et al. cGAS/STING axis mediates a topoisomerase II inhibitor-induced tumor immunogenicity. J. Clin. Invest. 129, 4850–4862 (2019).
pubmed: 31408442
pmcid: 6819145
Mollica, L. et al. Glycyrrhizin binds to high-mobility group box 1 protein and inhibits its cytokine activities. Chem. Biol. 14, 431–441 (2007).
pubmed: 17462578
Ohnishi, M. et al. HMGB1 inhibitor glycyrrhizin attenuates intracerebral hemorrhage-induced injury in rats. Neuropharmacology 61, 975–980 (2011).
pubmed: 21752338
Li, W. et al. EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages. Biochem. Pharmacol. 81, 1152–1163 (2011).
pubmed: 21371444
pmcid: 3072446
Horiuchi, T. et al. Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity. J. Biol. Chem. 292, 8436–8446 (2017).
pubmed: 28373282
pmcid: 5437248
Zhang, Y. et al. Tanshinone IIA sodium sulfonate facilitates endocytic HMGB1 uptake. Biochem. Pharmacol. 84, 1492–1500 (2012).
pubmed: 23022229
pmcid: 3491099
Tang, D. et al. Quercetin prevents LPS-induced high-mobility group box 1 release and proinflammatory function. Am. J. Respir. Cell Mol. Biol. 41, 651–660 (2009).
pubmed: 19265175
pmcid: 2784404
Lee, W., Ku, S. K., Bae, J. W. & Bae, J. S. Inhibitory effects of lycopene on HMGB1-mediated pro-inflammatory responses in both cellular and animal models. Food Chem. Toxicol. 50, 1826–1833 (2012).
pubmed: 22429818
Zainal, N. et al. Resveratrol treatment reveals a novel role for HMGB1 in regulation of the type 1 interferon response in dengue virus infection. Sci. Rep. 7, 42998 (2017).
pubmed: 28216632
pmcid: 5316936
Wang, H. et al. The aqueous extract of a popular herbal nutrient supplement, Angelica sinensis, protects mice against lethal endotoxemia and sepsis. J. Nutr. 136, 360–365 (2006).
pubmed: 16424112
Li, W. et al. A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1. J. Immunol. 178, 3856–3864 (2007).
pubmed: 17339485
Ulloa, L. et al. Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc. Natl Acad. Sci. USA 99, 12351–12356 (2002).
pubmed: 12209006
pmcid: 129448
Jin, D. et al. Atorvastatin reduces serum HMGB1 levels in patients with hyperlipidemia. Exp. Ther. Med. 4, 1124–1126 (2012).
pubmed: 23226786
pmcid: 3494102
Ostberg, T. et al. Oxaliplatin retains HMGB1 intranuclearly and ameliorates collagen type II-induced arthritis. Arthritis Res. Ther. 10, R1 (2008).
pubmed: 18179697
pmcid: 2374449
Pan, P. et al. Low-dose cisplatin administration in murine cecal ligation and puncture prevents the systemic release of HMGB1 and attenuates lethality. J. Leukoc. Biol. 86, 625–632 (2009).
pubmed: 19487305
Tsung, A. et al. Ethyl pyruvate ameliorates liver ischemia–reperfusion injury by decreasing hepatic necrosis and apoptosis. Transplantation 79, 196–204 (2005).
pubmed: 15665768
Turkyilmaz, S. et al. Ethyl pyruvate treatment ameliorates pancreatic damage: evidence from a rat model of acute necrotizing pancreatitis. Arch. Med. Sci. 15, 232–239 (2019).
pubmed: 30697275
Schierbeck, H. et al. Monoclonal anti-HMGB1 (high mobility group box chromosomal protein 1) antibody protection in two experimental arthritis models. Mol. Med. 17, 1039–1044 (2011).
pubmed: 21666956
pmcid: 3188862
Aulin, C., Lassacher, T., Palmblad, K. & Erlandsson Harris, H. Early stage blockade of the alarmin HMGB1 reduces cartilage destruction in experimental OA. Osteoarthr. Cartil. 28, 698–707 (2020).
Nishibori, M., Mori, S. & Takahashi, H. K. Anti-HMGB1 monoclonal antibody therapy for a wide range of CNS and PNS diseases. J. Pharmacol. Sci. 140, 94–101 (2019).
pubmed: 31105025
Zickert, A. et al. Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis. Arthritis Res. Ther. 14, R36 (2012).
pubmed: 22348591
pmcid: 3392835
Schaper, F. et al. Treatment with anti-HMGB1 monoclonal antibody does not affect lupus nephritis in MRL/lpr mice. Mol. Med. 22, 12–21 (2016).
pubmed: 26837069
pmcid: 5004709
Muire, P. J., Avila, J. J., Lofgren, A. L. & Wenke, J. C. Neutralization of HMGB1 improves fracture healing and gammadelta T lymphocyte counts at the fracture site in a polytrauma rat model. J. Exp. Orthop. 9, 21 (2022).
pubmed: 35229226
pmcid: 8885932
Son, M. et al. C1q and HMGB1 reciprocally regulate human macrophage polarization. Blood 128, 2218–2228 (2016).
pubmed: 27683415
pmcid: 5095756
Ito, T. et al. Proteolytic cleavage of high mobility group box 1 protein by thrombin–thrombomodulin complexes. Arterioscler. Thromb. Vasc. Biol. 28, 1825–1830 (2008).
pubmed: 18599803
Tang, Y. et al. Heparin prevents caspase-11-dependent septic lethality independent of anticoagulant properties. Immunity 54, 454–467.e6 (2021).
pubmed: 33561388
Yang, H. et al. Identification of CD163 as an antiinflammatory receptor for HMGB1–haptoglobin complexes. JCI Insight 1, e85375 (2016).
pubmed: 27294203
pmcid: 4902170
Avgousti, D. C. et al. A core viral protein binds host nucleosomes to sequester immune danger signals. Nature 535, 173–177 (2016).
pubmed: 27362237
pmcid: 4950998
Qiang, X. et al. Monoclonal antibodies capable of binding SARS-CoV-2 spike protein receptor-binding motif specifically prevent GM-CSF induction. J. Leukoc. Biol. 111, 261–267 (2022).
pubmed: 33759207
Chen, R. et al. HMGB1 as a potential biomarker and therapeutic target for severe COVID-19. Heliyon 6, e05672 (2020).
pubmed: 33313438
pmcid: 7720697
Musumeci, D. et al. DNA-based strategies for blocking HMGB1 cytokine activity: design, synthesis and preliminary in vitro/in vivo assays of DNA and DNA-like duplexes. Mol. Biosyst. 7, 1742–1752 (2011).
pubmed: 21431162
Yanai, H. et al. Suppression of immune responses by nonimmunogenic oligodeoxynucleotides with high affinity for high-mobility group box proteins (HMGBs). Proc. Natl Acad. Sci. USA 108, 11542–11547 (2011).
pubmed: 21709231
pmcid: 3136288
Ju, Z. et al. Sequestering HMGB1 via DNA-conjugated beads ameliorates murine colitis. PLoS ONE 9, e103992 (2014).
pubmed: 25127031
pmcid: 4134190
Wang, H. et al. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421, 384–388 (2003).
pubmed: 12508119
Rosas-Ballina, M. et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334, 98–101 (2011).
pubmed: 21921156
pmcid: 4548937
Huston, J. M. et al. Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit. Care Med. 35, 2762–2768 (2007).
pubmed: 17901837
Sitapara, R. A. et al. The alpha7 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. Mol. Med. 26, 63 (2020).
pubmed: 32600307
pmcid: 7322715
Pavlov, V. A. et al. Selective alpha7-nicotinic acetylcholine receptor agonist GTS-21 improves survival in murine endotoxemia and severe sepsis. Crit. Care Med. 35, 1139–1144 (2007).
pubmed: 17334244
Kang, R. et al. A novel PINK1- and PARK2-dependent protective neuroimmune pathway in lethal sepsis. Autophagy 12, 2374–2385 (2016).
pubmed: 27754761
pmcid: 5173260
Yan, Y. et al. Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell 160, 62–73 (2015).
pubmed: 25594175
Liu, S. et al. A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis. Nature 598, 641–645 (2021).
pubmed: 34646018
pmcid: 9178665
Chen, R., Kang, R. & Tang, D. The mechanism of HMGB1 secretion and release. Exp. Mol. Med. 54, 91–102 (2022).
pubmed: 35217834
pmcid: 8894452
Bonaldi, T. et al. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 22, 5551–5560 (2003).
pubmed: 14532127
pmcid: 213771
Qian, W. et al. Hypoxic ASCs-derived exosomes attenuate colitis by regulating macrophage polarization via miR-216a-5p/HMGB1 axis. Inflamm. Bowel Dis. 29, 602–619 (2023).
pubmed: 36287066
Zhao, Y. et al. Cardiopulmonary bypass-derived plasma exosomal HMGB1 contributes to alveolar epithelial cell necroptosis via mtDNA/cGAS/STING pathway. Shock 58, 534–541 (2022).
pubmed: 36516451
Oh, Y. J. et al. HMGB1 is phosphorylated by classical protein kinase C and is secreted by a calcium-dependent mechanism. J. Immunol. 182, 5800–5809 (2009).
pubmed: 19380828
Yang, Z. et al. PARP-1 mediates LPS-induced HMGB1 release by macrophages through regulation of HMGB1 acetylation. J. Immunol. 193, 6114–6123 (2014).
pubmed: 25392528
Xie, M. et al. PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nat. Commun. 7, 13280 (2016).
pubmed: 27779186
pmcid: 5093342
Orning, P. et al. Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death. Science 362, 1064–1069 (2018).
pubmed: 30361383
pmcid: 6522129
Chen, H. et al. RIPK3 collaborates with GSDMD to drive tissue injury in lethal polymicrobial sepsis. Cell Death Differ. 27, 2568–2585 (2020).
pubmed: 32152555
pmcid: 7429874
Turubanova, V. D. et al. Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine. J. Immunother. Cancer 7, 350 (2019).
pubmed: 31842994
pmcid: 6916435
Wei, J. et al. Genome-wide CRISPR screens reveal host factors critical for SARS-CoV-2 infection. Cell 184, 76–91.e13 (2021).
pubmed: 33147444
Satish, M., Gunasekar, P., Asensio, J. A. & Agrawal, D. K. Vitamin D attenuates HMGB1-mediated neointimal hyperplasia after percutaneous coronary intervention in swine. Mol. Cell. Biochem. 474, 219–228 (2020).
pubmed: 32737774
pmcid: 7530059
Vogel, S. et al. The platelet NLRP3 inflammasome is upregulated in sickle cell disease via HMGB1/TLR4 and Bruton tyrosine kinase. Blood Adv. 2, 2672–2680 (2018).
pubmed: 30333099
pmcid: 6199654
Careccia, G. et al. Rebalancing expression of HMGB1 redox isoforms to counteract muscular dystrophy. Sci. Transl. Med. 13, eaay8416 (2021).
pubmed: 34078746
Chen, L. et al. Elevated serum levels of S100A8/A9 and HMGB1 at hospital admission are correlated with inferior clinical outcomes in COVID-19 patients. Cell Mol. Immunol. 17, 992–994 (2020).
pubmed: 32620787
Cai, J. & Lin, Z. Correlation of blood high mobility group box-1 protein with mortality of patients with sepsis: a meta-analysis. Heart Lung 50, 885–892 (2021).
pubmed: 34411870
Angus, D. C. et al. Circulating high-mobility group box 1 (HMGB1) concentrations are elevated in both uncomplicated pneumonia and pneumonia with severe sepsis. Crit. Care Med. 35, 1061–1067 (2007).
pubmed: 17334246
Gaini, S., Koldkjaer, O. G., Moller, H. J., Pedersen, C. & Pedersen, S. S. A comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study. Crit. Care 11, R76 (2007).
pubmed: 17625012
pmcid: 2206511
Barnay-Verdier, S. et al. Emergence of autoantibodies to HMGB1 is associated with survival in patients with septic shock. Intensive Care Med. 37, 957–962 (2011).
pubmed: 21359606
Gamez-Diaz, L. Y. et al. Diagnostic accuracy of HMGB-1, sTREM-1, and CD64 as markers of sepsis in patients recently admitted to the emergency department. Acad. Emerg. Med. 18, 807–815 (2011).
pubmed: 21762470
Pang, X. et al. Expression and effects of high-mobility group box 1 in cervical cancer. Int. J. Mol. Sci. 15, 8699–8712 (2014).
pubmed: 24837834
pmcid: 4057754
Sun, S. et al. High mobility group box-1 and its clinical value in breast cancer. Onco Targets Ther. 8, 413–419 (2015).
pubmed: 25709474
pmcid: 4334343
Chen, S. et al. Hepatitis B virus X protein stimulates high mobility group box 1 secretion and enhances hepatocellular carcinoma metastasis. Cancer Lett. 394, 22–32 (2017).
pubmed: 28216372
Liikanen, I. et al. Serum HMGB1 is a predictive and prognostic biomarker for oncolytic immunotherapy. Oncoimmunology 4, e989771 (2015).
pubmed: 25949903
pmcid: 4404794