HMGB1 Is a Therapeutic Target for Sterile Inflammation and Infection

By U. Andersson, Kevin J. Tracey. Annual Review of Immunology, 2011

1,416 citations recorded by the source corpus.

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.

Subfields: Clinical Biochemistry, Immunology

View Paper: https://www.semanticscholar.org/paper/ec7afc54997b8a06a81341737c99fdc58a1710e4

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Clinical Biochemistry

1. Kevin J. Tracey
2. D. Tang
3. R. Kang
4. Michael Lotze
5. H. J. Zeh
6. U. Andersson
7. M. Bianchi
8. C. Deutschman

In Immunology

1. Kevin J. Tracey
2. Michael Lotze
3. D. Tang
4. R. Kang
5. H. J. Zeh
6. U. Andersson
7. M. Bianchi
8. C. Deutschman

Citations in the corpus

• The role of oxidative stress during inflammatory processes (2013, background): “…myocardial infarction (Loukili et  al., 2011), hepatic ischemia (Tsung et  al., 2005), stroke (Schulze et al., 2013), circulatory shock and trauma (Andersson and Tracey, 2011), diabetes (Nogueira-Machado et  al., 2011), cancer (Krysko et  al., 2012), and arthritis (Harris et  al., 2012), and…”
• PAMPs and DAMPs: Signal 0s that Spur Autophagy and Immunity (2012, background): “The HMGB1 protein induces migration and activation of human dendritic cells (DCs), eosinophil, natural killer (NK)-DC cross-talk, and T-cell activation (70, 71).”
• Sepsis: current dogma and new perspectives. (2014, background): “Serum HMGB1 accumulation in response to infection or injury is nearly universally found in animal studies and clinical investigations of severe sepsis Immunity 40, April 17, 2014 ª2014 Elsevier Inc. 469 (Angus et al., 2007; Andersson and Tracey, 2011; Wang et al., 2004; Wang et al., 2004).”
• Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β (2011, background): “HMGB1 is a major proinflammatory alarmin or DAMP (damage-associated molecular pattern) normally present in the nucleus (Andersson and Tracey, 2011).”
• Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release (2012, background): “Notably, immune cells secrete HMGB1 when activated by infection or tissue damage (Andersson and Tracey, 2011); mesothelioma and other cancer cells secrete HMGB1 constitutively (Jube et al., 2012).”
• DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation. (2020, neutral): “HMGB1 TLR2, TLR4, TLR9, RAGE, CD24 (132) Neutralizing antibodies, TLR4 antagonists (133)”