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HMGB1 is a nuclear protein that is released passively by necrotic cells, retained by apoptotic cells, and secreted actively by inflammatory cells (Dumitriu et al. HMGB1: guiding immunity from within. Trends Immunol 2005, 26: 381-7). HMGB1 is essential for life: Hmgb1 knockout mice die shortly after birth.
The two different activities of HMGB1 as a chemoattractanct of motile cells and as inducer of cytokines have been attributed to different biochemical forms. Fully reduced HMGB1 (the form with chemoattractanct activity) is completely reduced; disulfide HMGB1 contains a disulfide bond between C23 and C45 (complete notation: HMGB1C23-C45C106h - Antoine J. et al (2014).Mol Med).
Disulfide HMGB1 can induce cytokine and chemokine production in monocytes and other inflammatory cells (Venereau et al, 2012).
Structurally, Disulfide HMGB1 has a disulfide bridge between cysteine residues 23 and 45 and a reduced cysteine residue 106. Disulfide HMGB1 is tested for the ability to stimulate cytokine production in human macrophages.