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Table 2 Isoforms of HMGB1 and MD-2 binding and cytokine/chemokine activity.

From: High Mobility Group Box Protein 1 (HMGB1): The Prototypical Endogenous Danger Molecule

HMGB1 isoforms

MD-2 binding

Cytokine activity

Chemokine activity

Disulfide

+

+

−

Hg-modified

−

−

−

Fully reduced

−

−

+

H2S-modified

−

−

−

Sulfonyl

−

−

−

  1. Isoforms of HMGB1, generated by a synthetic formation of mercury thiolate on C106 (Hg-modified), by S-sulfhydration (H2S) to convert cysteine thiol (−SH) group to −SSH (H2S-modified), by exposure to reducing agent dithiothreitol (fully reduced) or oxidized by hydrogen peroxide (sulfonyl), were tested for their MD-2-binding via Biosensor-based surface plasmon resonance analysis (BIAcore) (3). Only disulfide HMGB1 binds to MD-2 and induced TNF secretion. Fully reduced HMGB1 has chemokine activity.