Oxidation of HMGB1 Is a Dynamically Regulated Process in Physiological and Pathological Conditions.

Frontiers in Immunology
Michele FerraraEmilie Venereau

Abstract

Acute inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens or cell damage, and is essential for immune defense and proper healing. However, unresolved inflammation can lead to chronic disorders, including cancer and fibrosis. The High Mobility Group Box 1 (HMGB1) protein is a Damage-Associated Molecular Pattern (DAMP) molecule that orchestrates key events in inflammation by switching among mutually exclusive redox states. Fully reduced HMGB1 (frHMGB1) supports immune cell recruitment and tissue regeneration, while the isoform containing a disulphide bond (dsHMGB1) promotes secretion of inflammatory mediators by immune cells. Although it has been suggested that the tissue itself determines the redox state of the extracellular space and of released HMGB1, the dynamics of HMGB1 oxidation in health and disease are unknown. In the present work, we analyzed the expression of HMGB1 redox isoforms in different inflammatory conditions in skeletal muscle, from acute injury to muscle wasting, in tumor microenvironment, in spleen, and in liver after drug intoxication. Our results reveal that the redox modulation of HMGB1 is tissue-specific, with high expression of dsHMGB1 in normal spleen and liver...Continue Reading

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Citations

Jul 16, 2020·Cells·Bernardo L RapoportRonald Anderson
Dec 2, 2020·Cells·Giorgio AquilaRosanna Piccirillo
Oct 30, 2020·International Journal of Molecular Sciences·Elena ChikhirzhinaAlexey Tomilin
Apr 30, 2021·Frontiers in Cell and Developmental Biology·Vincenza FrisardiMaria Elisabeth Street
Jun 4, 2021·Science Translational Medicine·Giorgia CarecciaEmilie Vénéreau
Jun 9, 2021·Molecular Medicine·Huan YangKevin J Tracey

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Methods Mentioned

BETA
protein Assay
ELISA
acetylation
protein folding

Software Mentioned

GraphPad
ImageJ
Prism
Imaris

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