Zhu Shu, Li Wei, Ward Mary F, Sama Andrew E, Wang Haichao
The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
Inflamm Allergy Drug Targets. 2010 Mar;9(1):60-72. doi: 10.2174/187152810791292872.
In response to infection or injury, a ubiquitous nucleosomal protein, HMGB1 is secreted actively by innate immune cells, and / or released passively by injured/damaged cells. Subsequently, extracellular HMGB1 alerts, recruits, and activates various innate immune cells to sustain a rigorous inflammatory response. A growing number of HMGB1 inhibitors ranging from neutralizing antibodies, endogenous hormones, to medicinal herb-derived small molecule HMGB1 inhibitors (such as nicotine, glycyrrhizin, tanshinones, and EGCG) are proven protective against lethal infection and ischemic injury. Here we review emerging evidence that support extracellular HMGB1 as a proinflammatory alarmin(g) danger signal, and discuss a wide array of HMGB1 inhibitors as potential therapeutic agents for sepsis and ischemic injury.
作为对感染或损伤的反应，一种普遍存在的核小体蛋白HMGB1由先天免疫细胞主动分泌，和/或由受损细胞被动释放。随后，细胞外HMGB1警示、募集并激活各种先天免疫细胞，以维持强烈的炎症反应。越来越多的HMGB1抑制剂，从中和抗体、内源性激素到草药衍生的小分子HMGB1抑制剂（如尼古丁、甘草酸、丹参酮和表没食子儿茶素没食子酸酯），已被证明对致死性感染和缺血性损伤具有保护作用。在此，我们综述支持细胞外HMGB1作为促炎警报素（危险信号）的新证据，并讨论多种HMGB1抑制剂作为脓毒症和缺血性损伤潜在治疗药物的情况。
