HMGB1: endogenous danger signaling.
HMGB1: endogenous danger signaling.
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HMGB1：内源性危险信号。
DOI：
10.2119/2008-00034.klune
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发表时间：
2008-07
影响因子：
5.7
通讯作者：
Tsung, Allan
中科院分区：
文献类型：
--
作者：
Klune, John R.;Dhupar, Rajeev;Cardinal, Jon;Billiar, Timothy R.;Tsung, Allan
虽然外源病原体及其产物长期以来一直被认为可以激活先天免疫系统，但最近对一组具有类似功能的内源性分子的认识为理解病原体激活的炎症反应与损伤之间的重叠提供了一个框架。这些内源性分子，称为alarmins，是正常细胞成分，可以在细胞应激或损伤状态期间释放到细胞外环境中，随后激活免疫系统。一种核蛋白，高迁移率族蛋白-1（HMGB 1），由于通过参与感染性和非感染性炎症状态来实现警报素的功能而受到特别关注。一旦释放，HMGB 1通过各种受体发出信号，激活参与免疫过程的免疫细胞。虽然最初的研究表明HMGB 1是脓毒症的晚期介质，但最近的研究结果表明HMGB 1在非感染性炎症模型中具有重要作用，如自身免疫，癌症，创伤和缺血再灌注损伤。此外，与其促炎功能相反，有证据表明HMGB 1也具有导致组织修复和再生的恢复作用。HMGB 1作为一种典型的报警蛋白的复杂功能在这里概述，以审查我们目前对一种在许多重要的人类疾病中具有治疗潜力的分子的理解。
While foreign pathogens and their products have long been known to activate the innate immune system, the recent recognition of a group of endogenous molecules that serve a similar function has provided a framework for understanding the overlap between the inflammatory responses activated by pathogens and injury. These endogenous molecules, termed alarmins, are normal cell constituents that can be released into the extracellular milieu during states of cellular stress or damage and subsequently activate the immune system. One nuclear protein, High mobility group box-1 (HMGB1), has received particular attention as fulfilling the functions of an alarmin by being involved in both infectious and non-infectious inflammatory conditions. Once released, HMGB1 signals through various receptors to activate immune cells involved in the immune process. Although initial studies demonstrated HMGB1 as a late mediator of sepsis, recent findings indicate HMGB1 to have an important role in models of non-infectious inflammation, such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. Furthermore, in contrast to its pro-inflammatory functions, there is evidence that HMGB1 also has restorative effects leading to tissue repair and regeneration. The complex functions of HMGB1 as an archetypical alarmin are outlined here to review our current understanding of a molecule that holds the potential for treatment in many important human conditions.