Rider Peleg, Voronov Elena, Dinarello Charles A, Apte Ron N, Cohen Idan
Department of Clinical Biochemistry and Pharmacology, Ben Gurion University of the Negev, 84105 Beer-Sheva, Israel.
The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben Gurion University of the Negev, 84105 Beer-Sheva, Israel.
J Immunol. 2017 Feb 15;198(4):1395-1402. doi: 10.4049/jimmunol.1601342.
Over the last decade, danger-associated molecular pattern molecules, or alarmins, have been recognized as signaling mediators of sterile inflammatory responses after trauma and injury. In contrast with the accepted passive release models suggested by the "danger hypothesis," it was recently shown that alarmins can also directly sense and report damage by signaling to the environment when released from live cells undergoing physiological stress, even without loss of subcellular compartmentalization. In this article, we review the involvement of alarmins such as IL-1α, IL-33, IL-16, and high-mobility group box 1 in cellular and physiological stress, and suggest a novel activity of these molecules as central initiators of sterile inflammation in response to nonlethal stress, a function we denote "stressorins." We highlight the role of posttranslational modifications of stressorins as key regulators of their activity and propose that targeted inhibition of stressorins or their modifiers could serve as attractive new anti-inflammatory treatments for a broad range of diseases.
在过去十年中，危险相关分子模式分子，即警报素，已被确认为创伤和损伤后无菌性炎症反应的信号介质。与“危险假说”提出的公认的被动释放模型不同，最近有研究表明，警报素在从经历生理应激的活细胞中释放时，即使没有亚细胞区室化的丧失，也能通过向环境发出信号直接感知并报告损伤。在本文中，我们综述了白细胞介素-1α、白细胞介素-33、白细胞介素-16和高迁移率族蛋白B1等警报素在细胞和生理应激中的作用，并提出这些分子作为非致死性应激下无菌性炎症的核心启动子的新活性，我们将这一功能称为“应激素”。我们强调应激素的翻译后修饰作为其活性关键调节因子的作用，并提出靶向抑制应激素或其修饰剂可作为治疗多种疾病的有吸引力的新型抗炎疗法。
