High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease.

Journal Article (Journal Article;Review)

High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 can serve as an alarmin to activate the innate system and mediate a wide range of physiological and pathological responses. To function as an alarmin, HMGB1 translocates from the nucleus of the cell to the extra-cellular milieu, a process that can take place with cell activation as well as cell death. HMGB1 can interact with receptors that include RAGE (receptor for advanced glycation endproducts) as well as Toll-like receptor-2 (TLR-2) and TLR-4 and function in a synergistic fashion with other proinflammatory mediators to induce responses. As shown in studies on patients as well as animal models, HMGB1 can play an important role in the pathogenesis of rheumatic disease, including rheumatoid arthritis, systemic lupus erythematosus, and polymyositis among others. New approaches to therapy for these diseases may involve strategies to inhibit HMGB1 release from cells, its interaction with receptors, and downstream signaling.

Full Text

Duke Authors

Cited Authors

  • Pisetsky, DS; Erlandsson-Harris, H; Andersson, U

Published Date

  • 2008

Published In

Volume / Issue

  • 10 / 3

Start / End Page

  • 209 -

PubMed ID

  • 18598385

Pubmed Central ID

  • PMC2483460

Electronic International Standard Serial Number (EISSN)

  • 1478-6362

Digital Object Identifier (DOI)

  • 10.1186/ar2440


  • eng

Conference Location

  • England