HMGB1: Endogenous Danger Signaling

By J. Klune, R. Dhupar, Jon S. Cardinal, Timothy R. Billiar, A. Tsung. Molecular Medicine, 2008

788 citations recorded by the source corpus.

While foreign pathogens and their products have long been known to activate the innate immune system, the recent recognition of a group of endogenous molecules that serve a similar function has provided a framework for understanding the overlap between the inflammatory responses activated by pathogens and injury. These endogenous molecules, termed alarmins, are normal cell constituents that can be released into the extracellular milieu during states of cellular stress or damage and subsequently activate the immune system. One nuclear protein, High mobility group box-1 (HMGB1), has received particular attention as fulfilling the functions of an alarmin by being involved in both infectious and non-infectious inflammatory conditions. Once released, HMGB1 signals through various receptors to activate immune cells involved in the immune process. Although initial studies demonstrated HMGB1 as a late mediator of sepsis, recent findings indicate HMGB1 to have an important role in models of non-infectious inflammation, such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. Furthermore, in contrast to its pro-inflammatory functions, there is evidence that HMGB1 also has restorative effects leading to tissue repair and regeneration. The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions.

Subfields: Clinical Biochemistry, Immunology

View Paper: https://www.semanticscholar.org/paper/7b5ae07b62c867eff99fdb60cb3b07c8c8aeee88

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. U. Andersson
3. N. Pitman
4. I. McInnes
5. F. Liew

In Immunology

1. Kevin J. Tracey
2. U. Andersson
3. I. McInnes
4. F. Liew

Citations in the corpus

• Damage-Associated Molecular Patterns in Inflammatory Diseases (2018, background): “The levels of HMGB1 and soluble RAGE are significantly elevated in the sera of AD patients, which was correlated with the levels of amyloid beta (75).”
• Disease-associated functions of IL-33: the new kid in the IL-1 family (2010, background): “Another protein with similarities to IL-33 is high mobility group box 1 ( HMGB1”
• HMGB1 Is a Therapeutic Target for Sterile Inflammation and Infection (2011, background): “The preponderance of data from animal models of ischemia and HMGB1 directly implicate TLR4 as the receptor that mediates cytokine release and resultant tissue damage (6, 26, 117).”
• Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015, background): “…in vivo and in vitro studies have reported that the increase in hyaluronic acid synthesis after parathyroid hormone (PTH) treatment was related to a subsequent bone resorption [123–127] suggesting a possible relationship between hyaluronic acid synthesis and the increase in osteoclast activity.”