Mechanisms of Disease: the role of high-mobility group protein 1 in the pathogenesis of inflammatory arthritis.


Journal Article (Review)

High-mobility group protein 1 (HMG1) is a nonhistone nuclear protein that is a prototype of a dual-function alarmin whose immune activity is dependent upon its cellular location. Inside the cell, HMG1 binds to DNA and has a role in transcriptional regulation. Outside the cell, HMG1 acts as a cytokine and has activities that resemble those of tumor necrosis factor. The cytokine activities of HMG1 become manifest when this protein translocates from the nucleus to the cytoplasm and, eventually, into the external milieu; this translocation occurs during cell activation and cell death. Given its cytokine activity, HMG1 has been implicated in the pathogenesis of a broad range of immune-mediated diseases including arthritis. The role for this protein in arthritis was established by observations of the expression of HMG1 in synovial tissue of patients with rheumatoid arthritis as well as in the joints of animals used to model arthritis. Furthermore, in the mouse model of collagen-induced arthritis, treatment with antibodies to HMG1 or to an inhibitory domain of HMG1 can attenuate joint inflammation and damage. These studies identify a novel pathway in the pathogenesis of inflammatory arthritis, as well as a new target for biologic therapy.

Full Text

Duke Authors

Cited Authors

  • Jiang, W; Pisetsky, DS

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 3 / 1

Start / End Page

  • 52 - 58

PubMed ID

  • 17203009

Pubmed Central ID

  • 17203009

International Standard Serial Number (ISSN)

  • 1745-8382

Digital Object Identifier (DOI)

  • 10.1038/ncprheum0379


  • eng

Conference Location

  • United States