| HMGB1 represents a potential marker of disease activity and novel therapeutic target in SLE. | |
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MedLine Citation:
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PMID: 21793951 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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High-mobility group box 1 (HMGB1) protein is a nuclear DNA-binding protein, which functions as an alarmin when released from cells. Recent studies implicate extracellular HMGB1 in the pathogenesis of systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by the formation of multiple autoantibodies, especially those directed against nucleosomes and double stranded (ds)DNA. Elevated concentrations of HMGB1 are observed in sera as well as in skin lesions of patients with lupus. Of importance, serum HMGB1 and anti-HMGB1 autoantibody levels correlate with disease activity. In the blood of patients with SLE, HMGB1 is complexed with nucleosomes, at least partially. Moreover, HMGB1-nucleosome complexes from apoptotic cells activate antigen-presenting cells. Injection of HMGB1-nucleosome complexes into non-autoimmune mice results in the formation of autoantibodies against dsDNA and histones in a Toll-like receptor (TLR) 2-dependent manner. Additionally, HMGB1, as a part of DNA-anti-DNA immune complexes, can interact with receptor for advanced glycation end-products (RAGE) on the surface of plasmacytoid dendritic cells and B cells leading to TLR9-dependent interferon (IFN)α release and activation of autoreactive B cells, respectively. HMGB1 attached to neutrophil extracellular traps may contribute to IFNα production by facilitating the recognition of self nucleic acids. Furthermore, HMGB1, complexed with DNA and pathogenic anti-DNA autoantibodies, activates its receptors TLR2, TLR4 and RAGE, and may thereby be involved in anti-DNA autoantibody-induced kidney damage in lupus nephritis. Collectively, these findings suggest that HMGB1 is a potential marker of disease activity and, due to its probable involvement in the pathogenesis, a novel therapeutic target in SLE. |
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Authors:
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Vilma Urbonaviciute; Reinhard E Voll |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-27 |
Journal Detail:
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Title: Journal of internal medicine Volume: - ISSN: 1365-2796 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8904841 Medline TA: J Intern Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 The Association for the Publication of the Journal of Internal Medicine. |
Affiliation:
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Department Internal Medicine 3, Clinical Research Group, Nikolaus-Fiebiger Centre of Molecular Medicine, Friedrich-Alexander University of Erlangen-Nuremberg, Germany Department Rheumatology and Clinical Immunology & Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg/Breisgau, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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