HMGB1 loves company

J Leukoc Biol. 2009 Sep;86(3):573-6. doi: 10.1189/jlb.1008585. Epub 2009 May 4.


HMGB1, outside of a cell, is a trigger of inflammation and a stimulus for tissue reconstruction; the balance may depend on the complexes it forms with other molecules. HMGB1 is the prime example of a danger signal that originates from the damaged self rather than from invading pathogens. HMGB1 is released by cells that die traumatically and is secreted by cells destined to die and by activated cells of the innate immunity system. As a danger signal, HMGB1 is expected to trigger inflammation, but recent reports indicate that pure recombinant HMGB1 has no proinflammatory activity and only acts as a chemoattractant and a mitogen. However, HMGB1 forms highly inflammatory complexes with ssDNA, LPS, IL-1beta, and nucleosomes, which interact with TLR9, TLR4, IL-1R, and TLR2 receptors, respectively. Thus, HMGB1 has dual activities, solo or in company; I speculate that this may serve our body's necessity to sacrifice or reconstruct tissues as required by the presence or absence of pathogens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • Cell Proliferation / drug effects
  • DNA, Single-Stranded / immunology
  • HMGB1 Protein / genetics
  • HMGB1 Protein / immunology*
  • HMGB1 Protein / pharmacology
  • HMGB1 Protein / physiology
  • Humans
  • Immunity, Innate / immunology*
  • Inflammation / immunology*
  • Interleukin-1beta / immunology
  • Lipopolysaccharides / immunology
  • Nucleosomes / immunology
  • Protein Binding / immunology
  • Receptors, Interleukin-1 / immunology
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Signal Transduction
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 4 / immunology
  • Toll-Like Receptor 9 / immunology


  • DNA, Single-Stranded
  • HMGB1 Protein
  • Interleukin-1beta
  • Lipopolysaccharides
  • Nucleosomes
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9