Molecular Medicine

, Volume 21, Supplement 1, pp S6–S12 | Cite as

High Mobility Group Box Protein 1 (HMGB1): The Prototypical Endogenous Danger Molecule

  • Huan Yang
  • Haichao Wang
  • Sangeeta S. Chavan
  • Ulf Andersson
Invited Review Article


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.



This work was supported by grants from the National Institutes of Health (RO1GM098446 to H Yang and RO1AT005076 to H Wang).


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Authors and Affiliations

  • Huan Yang
    • 1
  • Haichao Wang
    • 2
  • Sangeeta S. Chavan
    • 1
  • Ulf Andersson
    • 3
  1. 1.Laboratory of Biomedical ScienceThe Feinstein Institute for Medical ResearchManhassetUSA
  2. 2.Laboratory of Emergency MedicineThe Feinstein Institute for Medical ResearchManhassetUSA
  3. 3.Department of Women’s and Children’s Health, Karolinska InstitutetKarolinska University HospitalStockholmSweden

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