High mobility group box 1 protein (HMGB1)

High mobility group box protein B (HMGB1) is an evolutionarily conserved non-histone nuclear protein encoded by the HMGB1 gene. It plays critical roles inside cells—organizing DNA structure, regulating transcription through chromatin remodeling—and outside cells where it acts as a prototypical alarmin/DAMP. Upon cell activation or injury (such as necrosis), HMGB1 translocates from nucleus to cytoplasm then is secreted into the extracellular space where it functions like a cytokine. Extracellularly released/secreted HMGB1 triggers inflammatory responses by binding pattern recognition receptors including TLRs (notably TLR2/TLR4), amplifying innate immunity during both sterile injury and infection. Its dysregulation contributes to pathogenesis across diverse conditions such as sepsis, autoimmune diseases (e.g., rheumatoid arthritis), cardiovascular disease (e.g., atherosclerosis), cancer immunity modulation, among others. Therapeutic strategies targeting extracellular HMGB1—such as neutralizing antibodies—are under investigation for their potential benefit in controlling excessive inflammation without compromising essential homeostatic functions.

Other names

high-mobility group protein 1HMG-1amphoterin

Neutralization of extracellular HMGB1 to reduce inflammation and tissue damage by blocking its interaction with receptors such as TLR2/TLR4. Modulation of immune response by interfering with DAMP signaling. Inhibition of downstream cytokine release from macrophages/monocytes.