High mobility group box 1 (HMGB1) is a protein highly conserved across species that is present in the nuclei (chromatin associated) and cytoplasm of all cells. In the cytoplasm, HMGB1 is a critical regulator of autophagy, enhances cell survival, and limits apoptosis. It also acts as a chaperone that reduces protein aggregation caused by heat or chemical stress. HMGB1 is released to the extracellular milieu by inflammatory cells and by necrotic and apoptotic cells. Once released, it functions as an inflammatory cytokine and it is secreted by macrophages and monocytes as a late response to LPS, TNF-α, IL-1β, or IFN-γ. Interestingly, the inflammatory activity of extracellular HMGB1 is dependent upon its redox state. The protein possesses three cysteine residues: C23, C45, and C106. In its reduced state, HMGB1, (-SH), has chemotactic activity; whereas HMGB1, with a disulfide bond between C23 and C45, induces cytokine production and the activation of NF-κB. The fully oxidized form has no immune function, losing its proinflammatory effect and the caspase-dependent apoptotic cell death activation function. HMGB1 interacts with several molecules, such as IL-1β, RNA, DNA, LPS, lipoteichoic acid (LTA), and CXCL12. Thus, HMGB1 displays greater proinflammatory activity through cytokine binding, and the chemotactic property is mediated by CXCL12 binding. Extracellular HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases, which include: sepsis, rheumatoid arthritis, atherosclerosis, chronic kidney disease, systemic lupus erythematosus, and cancer. It has also been associated to chronic pain and delayed gastric ulcer healing in mice.
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Biolegend 人重組蛋白HMGB1 557804
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