Novel insights for high mobility group box 1 proteinmediated cellular immune response in sepsis:A systemic review

BACKGROUND:High mobility group box 1 protein(HMGB1) is a highly conserved,ubiquitous protein in the nuclei and cytoplasm of nearly all cell types.HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine.In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis.METHODS:This systemic review is mainly based on our own work and other related reports.RESULTS:HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes,regulatory T cells(Tregs),dendritic cells(DCs),macrophages,and natural killer cells(NK cells).Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors[e.g.,the receptor for advanced glycation end products(RAGE),Toll-like receptor(TLR)2,and TLR4].Anti-HMGB1 treatment,such as anti-HMGB1 polyclonal or monoclonal antibodies,inhibitors(e.g.,ethyl pyruvate) and antagonists(e.g.,A box),can protect against sepsis lethality and give a wider window for the treatment opportunity.CONCLUSION:HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.

High mobility group box 1 protein （HMGB1） is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. This systemic review is mainly based on our own work and other related reports HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells （Tregs）, dendritic cells （DCs）, macrophages, and natural killer cells （NK cells）. Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products （RAGE）, Toll-like receptor （TLR）2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors （e.g., ethyl pyruvate） and antagonists （e.g., A box）, can protect against sepsis lethality and give a wider window for the treatment opportunity. HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.