Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
J Intern Med. 2014 Nov;276(5):425-43. doi: 10.1111/joim.12276.
High-mobility group box 1 (HMGB1) was originally defined as a ubiquitous nuclear protein, but it was later determined that the protein has different roles both inside and outside of cells. Nuclear HMGB1 regulates chromatin structure and gene transcription, whereas cytosolic HMGB1 is involved in inflammasome activation and autophagy. Extracellular HMGB1 has drawn attention because it can bind to related cell signalling transduction receptors, such as the receptor for advanced glycation end products, Toll-like receptor (TLR)2, TLR4 and TLR9. It also participates in the development and progression of a variety of diseases. HMGB1 is actively secreted by stimulation of the innate immune system, and it is passively released by ischaemia or cell injury. This review focuses on the important role of HMGB1 in the pathogenesis of acute and chronic sterile inflammatory conditions. Strategies that target HMGB1 have been shown to significantly decrease inflammation in several disease models of sterile inflammation, and this may represent a promising clinical approach for treatment of certain conditions associated with sterile inflammation.
高迁移率族蛋白 B1（HMGB1）最初被定义为一种普遍存在的核蛋白，但后来发现该蛋白在细胞内外具有不同的作用。核 HMGB1 调节染色质结构和基因转录，而胞质 HMGB1 参与炎症小体激活和自噬。细胞外 HMGB1 引起了人们的关注，因为它可以与相关的细胞信号转导受体结合，如晚期糖基化终产物受体、Toll 样受体 (TLR)2、TLR4 和 TLR9。它还参与了多种疾病的发展和进展。HMGB1 可被固有免疫系统的刺激主动分泌，也可因缺血或细胞损伤而被动释放。这篇综述重点介绍了 HMGB1 在急性和慢性非感染性炎症发病机制中的重要作用。靶向 HMGB1 的策略已被证明可显著减轻几种非感染性炎症疾病模型中的炎症，这可能代表治疗与非感染性炎症相关的某些疾病的一种有前途的临床方法。
