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

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

By: William Parrish², Luis Ulloa²

Abstract

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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.

Affiliation(s): (2) North Shore University Hospital, Manhasset, NY

Book Title: Target Discovery and Validation Reviews and Protocols: Volume 2: Emerging Molecular Targets and Treatment Options

Series: Methods in Molecular Biology | Volume: 361 | Pub. Date: Feb-05-2007 | Page Range: 145-162 | DOI: 10.1385/1-59745-208-4:145

Subject: Pharmacology/Toxicology

Key Words: HMGB1 - proinflammatory cytokines - sepsis - posttranslational modifications

References

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