HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease.

Published online

Journal Article (Review)

HMGB1 is a non-histone nuclear protein that can serve as an alarmin to drive the pathogenesis of inflammatory and autoimmune disease. Although primarily located in the cell nucleus, HMGB1 can translocate to the cytoplasm, as well as the extracellular space, during cell activation and cell death; during activation, HMGB1 can undergo post-translational modifications. The activity of HMGB1 varies with the redox states of the cysteine residues, which are required for binding to TLR4. In addition to stimulating cells directly, HMGB1 can form immunostimulatory complexes with cytokines and other endogenous and exogenous factors. In the synovia of patients with rheumatoid arthritis, as well as animal models of this disease, extranuclear expression of HMGB1 is increased and blockade of HMGB1 expression attenuates disease in animal models. In systemic lupus erythematosus, HMGB1 can be a component of immune complexes containing anti-DNA because of its interaction with DNA. In myositis, expression of HMGB1 is enhanced in inflamed muscle and can perturb muscle function. Together, these findings indicate that HMGB1 might be an important mediator and biomarker in rheumatic diseases as well as a target of new therapy.

Full Text

Duke Authors

Cited Authors

  • Harris, HE; Andersson, U; Pisetsky, DS

Published Date

  • January 31, 2012

Published In

Volume / Issue

  • 8 / 4

Start / End Page

  • 195 - 202

PubMed ID

  • 22293756

Pubmed Central ID

  • 22293756

Electronic International Standard Serial Number (EISSN)

  • 1759-4804

Digital Object Identifier (DOI)

  • 10.1038/nrrheum.2011.222

Language

  • eng

Conference Location

  • United States