HMGB1 is a therapeutic target for sterile inflammation and infection

Annu Rev Immunol. 2011;29:139-62. doi: 10.1146/annurev-immunol-030409-101323.

Abstract

A key question in immunology concerns how sterile injury activates innate immunity to mediate damaging inflammation in the absence of foreign invaders. The discovery that HMGB1, a ubiquitous nuclear protein, mediates the activation of innate immune responses led directly to the understanding that HMGB1 plays a critical role at the intersection of the host inflammatory response to sterile and infectious threat. HMGB1 is actively released by stimulation of the innate immune system with exogenous pathogen-derived molecules and is passively released by ischemia or cell injury in the absence of invasion. Established molecular mechanisms of HMGB1 binding and signaling through TLR4 reveal signaling pathways that mediate cytokine release and tissue damage. Experimental strategies that selectively target HMGB1 and TLR4 effectively reverse and prevent activation of innate immunity and significantly attenuate damage in diverse models of sterile and infection-induced threat.

Publication types

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

MeSH terms

  • Animals
  • Drug Delivery Systems
  • HMGB1 Protein / antagonists & inhibitors*
  • HMGB1 Protein / metabolism
  • Humans
  • Immunity, Innate
  • Infections / drug therapy*
  • Infections / metabolism
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Toll-Like Receptor 4 / metabolism

Substances

  • HMGB1 Protein
  • Toll-Like Receptor 4