The regulation of interleukin-6 implicates skeletal muscle as an integrative stress sensor and endocrine organ.
The regulation of interleukin-6 implicates skeletal muscle as an integrative stress sensor and endocrine organ.
复制标题
IL-6 的调节涉及骨骼肌作为综合压力传感器和内分泌器官。
DOI：
10.1113/expphysiol.2012.068189
复制
发表时间：
2013
影响因子：
2.7
通讯作者：
Clanton,ThomasL
中科院分区：
文献类型：
--
作者：
Welc,StevenS;Clanton,ThomasL
新发现·本次审查的主题是什么？这篇综述讨论了白细胞介素-6（IL-6）基因的调控，以及它是如何独特地建立起来，以响应骨骼肌中的应激信号。我们认为骨骼肌是一种“压力传感器”，通过释放高度活跃的内分泌和旁分泌蛋白质（如IL-6）来做出反应。这突出了哪些进步？最近关于IL-6基因在各种应激暴露中的调节的发现导致骨骼肌在危及生命的应激条件下出现了新的潜在作用。了解IL-6分泌和应激之间的关系可能会为疾病、失调、炎症和衰老的正常适应性反应提供新的见解。由于其能够产生和分泌多种细胞因子（肌因子）和其他蛋白质，骨骼肌已被确定为内分泌器官。迄今为止，肌因子主要是在运动或代谢挑战的反应中进行研究的;然而，许多观察结果表明，骨骼肌也可能在某些类别的内部或外部应激暴露时释放肌因子。内部应激信号包括氧化或亚硝化应激、受损或未折叠的蛋白质、体温过高或能量失衡。作为生物应激或其他细胞损伤的指标的外部应激信号使用介质，如儿茶酚胺、内毒素、alarmin、ATP和促炎细胞因子，如肿瘤坏死因子-α和白细胞介素-1 β。外部应激信号通常通过膜受体系统诱导细胞反应。在这篇综述中，我们重点关注白细胞介素-6（IL-6）作为一种典型的应激反应肌因子的调节，并强调证据表明IL-6基因在肌肉中的调节是内在组织的，以应对各种各样的内部和外部压力。鉴于IL-6可以在危及生命的条件下启动整个生物体的保护，抗炎或恢复过程，我们提出骨骼肌具有作为压力传感器和反应器的生理功能的论点。此外，我们假设它可能包括一个有机体的急性应激反应的基本组成部分。
New findings•What is the topic of this review?This review discusses the regulation of the interleukin‐6 (IL‐6) gene and how it is uniquely set up to respond to stress signals in skeletal muscle. We propose that skeletal muscle is a ‘stress sensor’ that responds by releasing highly active endocrine and paracrine proteins, such as IL‐6.•What advances does this highlight?Recent discoveries on the regulation of theIL‐6gene in various stress exposures have resulted in the emergence of a new potential role for skeletal muscle in life‐threatening stress conditions. Understanding the relationship between IL‐6 secretion and stress may provide new insights into normal adaptive responses to disease, deconditioning, inflammation and ageing.Skeletal muscle has been identified as an endocrine organ owing to its capacity to produce and secrete a variety of cytokines (myokines) and other proteins. To date, myokines have primarily been studied in response to exercise or metabolic challenges; however, numerous observations suggest that skeletal muscle may also release myokines in response to certain categories of internal or external stress exposure. Internal stress signals include oxidative or nitrosative stress, damaged or unfolded proteins, hyperthermia or energy imbalance. External stress signals, which act as indicators of organismal stress or injury in other cells, employ mediators such as catecholamines, endotoxin, alarmins, ATP and pro‐inflammatory cytokines, such as tumour necrosis factor‐α and interleukin‐1β. External stress signals generally induce cellular responses through membrane receptor systems. In this review, we focus on the regulation of interleukin‐6 (IL‐6) as a prototypical stress response myokine and highlight evidence thatIL‐6gene regulation in muscle is inherently organized to respond to a wide variety of internal and external stressors. Given that IL‐6 can initiate protective, anti‐inflammatory or restorative processes throughout the organism during life‐threatening conditions, we present the argument that skeletal muscle has a physiological function as a sensor and responder to stress. Furthermore, we hypothesize that it may comprise a fundamental component of the organism's acute stress response.