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High-Mobility Group Box-1 Isoforms as Potential Therapeutic Targets in Sepsis

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Target Discovery and Validation Reviews and Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 361))

Abstract

High-mobility group box-1 (HMGB1) protein was originally described as a nuclear DNA-binding protein that functions as a structural cofactor critical for proper transcriptional regulation and gene expression. Recent studies indicate that damaged, necrotic cells liberate HMGB1 into the extracellular milieu where it functions as a proinflammatory cytokine. Indeed, HMGB1 represents a novel family of inflammatory cytokines composed of intracellular proteins that can be recognized by the innate immune system as a signal of tissue damage. Posttranslational modifications of HMGB1 determine its interactions with other proteins and modulate its biological activity. However, very little is known about how these posttranslational modifications of HMGB1 affect its extracellular inflammatory activity and pathological potential. These studies can provide more efficient therapeutic strategies directed against specific HMGB1 isoforms. Therapeutic strategies against these specific HMGB1 isoforms can serve as models for more efficient therapeutic strategies against rheumatoid arthritis or sepsis. This article reviews the recent studies on HMGB1 regulation and their impact on the inflammatory activity and pathological contribution of HMGB1 to infectious and inflammatory disorders.

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Authors and Affiliations

  1. North Shore University Hospital, Manhasset, NY

    William Parrish & Luis Ulloa

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  1. William Parrish
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  2. Luis Ulloa
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Editors and Affiliations

  1. Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway

    Mouldy Sioud

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© 2007 Humana Press Inc.

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Parrish, W., Ulloa, L. (2007). High-Mobility Group Box-1 Isoforms as Potential Therapeutic Targets in Sepsis. In: Sioud, M. (eds) Target Discovery and Validation Reviews and Protocols. Methods in Molecular Biology™, vol 361. Humana Press. https://doi.org/10.1385/1-59745-208-4:145

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  • DOI: https://doi.org/10.1385/1-59745-208-4:145

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-890-4

  • Online ISBN: 978-1-59745-208-3

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