Chen Yan, Li Guangping, Liu Yanxia, Werth Victoria P, Williams Kevin Jon, Liu Ming-Lin
Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
J Cell Physiol. 2016 Nov;231(11):2319-26. doi: 10.1002/jcp.25352. Epub 2016 Mar 9.
High mobility group box 1 (HMGB1) is a nuclear protein that can be released from activated or dead cells. Extracellular HMGB1 can serve as a "danger signal" and novel cytokine that mediates sterile inflammation. In addition to its soluble form, extracellular HMGB1 can also be carried by membrane microvesicles. However, the cellular mechanisms responsible for nuclear HMGB1 translocation to the plasma membrane and release onto membrane microvesicles have not been investigated. Tobacco smoking is a major cause of sterile inflammation in many diseases. Smoking also increases blood levels of HMGB1. In this study, we found that exposure of macrophages to tobacco smoke extract (TSE) stimulated HMGB1 expression, redistribution, and release into the extracellular milieu both as a soluble molecule and, surprisingly, as a microvesicle-associated form (TSE-MV). Inhibition of chromosome region maintenance-1 (CRM1), a nuclear exporter, attenuated TSE-induced HMGB1 redistribution from the nucleus to the cytoplasm, and then its release on TSE-MVs. Our study demonstrates a novel mechanism for the translocation of nuclear HMGB1 to the plasma membrane, and then its release in a microvesicle-associated form. J. Cell. Physiol. 231: 2319-2326, 2016. © 2016 Wiley Periodicals, Inc.
高迁移率族蛋白B1（HMGB1）是一种可从活化或死亡细胞中释放出来的核蛋白。细胞外HMGB1可作为一种“危险信号”和新型细胞因子，介导无菌性炎症。除了其可溶性形式外，细胞外HMGB1还可由膜微泡携带。然而，负责核HMGB1转运至质膜并释放到膜微泡上的细胞机制尚未得到研究。吸烟是许多疾病中无菌性炎症的主要原因。吸烟还会使血液中HMGB1水平升高。在本研究中，我们发现巨噬细胞暴露于烟草烟雾提取物（TSE）会刺激HMGB1的表达、重新分布，并以可溶性分子形式以及令人惊讶地以微泡相关形式（TSE-MV）释放到细胞外环境中。抑制核输出蛋白染色体区域维护蛋白1（CRM1）可减弱TSE诱导的HMGB1从细胞核到细胞质的重新分布，进而减弱其在TSE-MV上的释放。我们的研究证明了核HMGB1转运至质膜，然后以微泡相关形式释放的一种新机制。《细胞生理学杂志》231: 2319 - 2326, 2016年。© 2016威利期刊公司。
