HMGB1 is a therapeutic target for sterile inflammation and infection.
HMGB1 is a therapeutic target for sterile inflammation and infection.
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DOI：
10.1146/annurev-immunol-030409-101323
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发表时间：
2011
影响因子：
29.7
通讯作者：
Tracey KJ
中科院分区：
文献类型：
--
作者：
Andersson U;Tracey KJ
免疫学中的一个关键问题是无菌损伤如何激活先天免疫，在没有外来入侵者的情况下介导破坏性炎症。HMGB1是一种普遍存在的核蛋白，它介导先天免疫应答的激活，这一发现直接导致了HMGB1在宿主对无菌和感染性威胁的炎症应答的交叉点上发挥关键作用的理解。HMGB1通过用外源性病原体衍生分子刺激先天免疫系统而主动释放，并且在没有侵袭的情况下通过缺血或细胞损伤而被动释放。HMGB1通过TLR4结合和信号传导的分子机制揭示了介导细胞因子释放和组织损伤的信号传导途径。选择性靶向HMGB1和TLR4的实验策略有效地逆转和预防先天免疫的激活，并显着减弱各种不育和感染诱导的威胁模型中的损伤。
A key question in immunology concerns how sterile injury activates innate immunity to mediate damaging inflammation in the absence of foreign invaders. The discovery that HMGB1, a ubiquitous nuclear protein, mediates the activation of innate immune responses led directly to the understanding that HMGB1 plays a critical role at the intersection of the host inflammatory response to sterile and infectious threat. HMGB1 is actively released by stimulation of the innate immune system with exogenous pathogen-derived molecules and is passively released by ischemia or cell injury in the absence of invasion. Established molecular mechanisms of HMGB1 binding and signaling through TLR4 reveal signaling pathways that mediate cytokine release and tissue damage. Experimental strategies that selectively target HMGB1 and TLR4 effectively reverse and prevent activation of innate immunity and significantly attenuate damage in diverse models of sterile and infection-induced threat.