title: High Mobility Group Box Protein 1 (HMGB1): The Prototypical Endogenous Danger Molecule.
abstract: High mobility group box protein 1 (HMGB1) is an evolutionary ancient nuclear protein that exerts divergent biological tasks inside and outside of cells. The functions of HMGB1 depend on location, binding partners and redox states of the molecule. In the nucleus, HMGB1 organizes DNA and nucleosomes and regulates gene transcription. Upon cell activation or injury, nuclear HMGB1 can translocate to the cytoplasm, where it is involved in inflammasome activation and pyroptosis, as well as regulation of the autophagy/apoptosis balance. When actively secreted or passively released into the extracellular milieu, HMGB1 has cytokine, chemokine, neuroimmune and metabolic activities. Thus, HMGB1 plays multiple roles in the pathogenesis of inflammatory diseases and mediates immune responses that range from inflammation and bacterial killing to tissue repair. HMGB1 has been associated with divergent clinical conditions such as sepsis, rheumatoid arthritis and atherosclerosis. HMGB1 initiates and perpetuates immune responses during infectious and sterile inflammation, as the archetypical alarmin and damage-associated molecular pattern (DAMP) molecule. We here describe advances in the understanding of HMGB1 biology with focus on recent findings of its mission as a DAMP in danger sensing and as a therapeutic target in inflammatory diseases.
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Laboratory of Emergency Medicine, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Haichao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Sangeeta S
authors.initials: SS
authors.lastname: Chavan
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Andersson
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology; D007249:Inflammation; D009707:Nucleosomes / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000276:immunology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology; D018805:Sepsis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D058847:Inflammasomes; D009707:Nucleosomes; D000067759:Receptor for Advanced Glycation End Products; D019718:Receptors, CXCR4; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4