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The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases.

Publication ,  Journal Article
Magna, M; Pisetsky, DS
Published in: Mol Med
March 24, 2014

High-mobility group box 1 (HMGB1) protein is a highly abundant protein that can promote the pathogenesis of inflammatory and autoimmune diseases once it is in an extracellular location. This translocation can occur with immune cell activation as well as cell death, with the conditions for release associated with the expression of different isoforms. These isoforms result from post-translational modifications, with the redox states of three cysteines at positions 23, 45 and 106 critical for activity. Depending on the redox states of these residues, HMGB1 can induce cytokine production via toll-like receptor 4 (TLR4) or promote chemotaxis by binding the chemokine CXCL12 for stimulation via CXCR4. Fully oxidized HMGB1 is inactive. During the course of inflammatory disease, HMGB1 can therefore play a dynamic role depending on its redox state. As a mechanism to generate alarmins, cell death is an important source of HMGB1, although each major cell death form (necrosis, apoptosis, pyroptosis and NETosis) can lead to different isoforms of HMGB1 and variable levels of association of HMGB1 with nucleosomes. The association of HMGB1 with nucleosomes may contribute to the pathogenesis of systemic lupus erythematosus by producing nuclear material whose immunological properties are enhanced by the presence of an alarmin. Since HMGB1 levels in blood or tissue are elevated in many inflammatory and autoimmune diseases, this molecule can serve as a unique biomarker as well as represent a target of novel therapies to block its various activities.

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Published In

Mol Med

DOI

EISSN

1528-3658

Publication Date

March 24, 2014

Volume

20

Issue

1

Start / End Page

138 / 146

Location

England

Related Subject Headings

  • Toll-Like Receptor 4
  • Receptors, CXCR4
  • Protein Processing, Post-Translational
  • Protein Isoforms
  • Oxidation-Reduction
  • Nucleosomes
  • Inflammation
  • Immunology
  • Humans
  • HMGB1 Protein
 

Citation

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Magna, M., & Pisetsky, D. S. (2014). The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases. Mol Med, 20(1), 138–146. https://doi.org/10.2119/molmed.2013.00164
Magna, Melinda, and David S. Pisetsky. “The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases.Mol Med 20, no. 1 (March 24, 2014): 138–46. https://doi.org/10.2119/molmed.2013.00164.
Magna M, Pisetsky DS. The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases. Mol Med. 2014 Mar 24;20(1):138–46.
Magna, Melinda, and David S. Pisetsky. “The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases.Mol Med, vol. 20, no. 1, Mar. 2014, pp. 138–46. Pubmed, doi:10.2119/molmed.2013.00164.
Magna M, Pisetsky DS. The role of HMGB1 in the pathogenesis of inflammatory and autoimmune diseases. Mol Med. 2014 Mar 24;20(1):138–146.

Published In

Mol Med

DOI

EISSN

1528-3658

Publication Date

March 24, 2014

Volume

20

Issue

1

Start / End Page

138 / 146

Location

England

Related Subject Headings

  • Toll-Like Receptor 4
  • Receptors, CXCR4
  • Protein Processing, Post-Translational
  • Protein Isoforms
  • Oxidation-Reduction
  • Nucleosomes
  • Inflammation
  • Immunology
  • Humans
  • HMGB1 Protein