Roles of IL-6-gp130 Signaling in Vascular Inflammation.
Roles of IL-6-gp130 Signaling in Vascular Inflammation.
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DOI：
10.2174/157340308785160570
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发表时间：
2008-08
影响因子：
1.9
通讯作者：
Brasier AR
中科院分区：
文献类型：
--
作者：
Hou T;Tieu BC;Ray S;Recinos Iii A;Cui R;Tilton RG;Brasier AR
白细胞介素-6（IL-6）是多种不同类型心血管疾病和全因死亡率的公认独立指标。本文就IL-6及其通过糖蛋白130（gp 130）的信号通路在心血管稳态中的作用作一综述。通过血管紧张素II（Ang II）肽的作用，IL-6在血管组织中是高度可诱导的，其中它以旁分泌方式作用以通过两种不同的机制发出信号，第一种是经典的膜受体引发的途径，第二种是反式信号传导途径，即使在缺乏IL-6受体的组织中也能够诱导应答。本文介绍了其细胞内信号转导途径的最新进展和新概念，即Janus激酶（JAK）-信号转导和转录激活因子（STAT）。IL-6在多种心血管重要细胞类型中具有不同的作用，包括内皮细胞、单核细胞、血小板、肝细胞和脂肪细胞。我们讨论了IL-6在内皮功能障碍、通过影响单核细胞活化/分化引起的细胞炎症、活性氧（ROS）应激引起的细胞保护功能、促凝状态的调节、心肌生长控制及其在代谢控制和胰岛素抵抗中的作用。这些多重作用表明IL-6不仅仅是一种被动的生物标志物，而是主动调节对心血管应激的适应性和病理性反应。 IL-6是一种多功能细胞因子，其在循环中的存在与多种类型的心血管疾病有关，并且是动脉粥样硬化的独立危险因素。在这篇综述中，我们研究了IL-6信号的机制及其在心血管组织中调节血管炎症表现的无数作用。
Interleukin-6 (IL-6) is a well-established, independent indicator of multiple distinct types of cardiovascular disease and all-cause mortality. In this review, we present current understanding of the multiple roles that IL-6 and its signaling pathways through glycoprotein 130 (gp130) play in cardiovascular homeostasis. IL-6 is highly inducible in vascular tissues through the actions of the angiotensin II (Ang II) peptide, where it acts in a paracrine manner to signal through two distinct mechanisms, the first being a classic membrane receptor initiated pathway and the second, a trans-signaling pathway, being able to induce responses even in tissues lacking the IL-6 receptor. Recent advances and new concepts in how its intracellular signaling pathways operate via the Janus kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) are described. IL-6 has diverse actions in multiple cell types of cardiovascular importance, including endothelial cells, monocytes, platelets, hepatocytes and adipocytes. We discuss central roles of IL-6 in endothelial dysfunction, cellular inflammation by affecting monocyte activation/differentiation, cellular cytoprotective functions from reactive oxygen species (ROS) stress, modulation of pro-coagulant state, myocardial growth control, and its implications in metabolic control and insulin resistance. These multiple actions indicate that IL-6 is not merely a passive biomarker, but actively modulates adaptive and pathological responses to cardiovascular stress. IL-6 is a multifunctional cytokine whose presence in the circulation is linked with diverse types of cardiovascular disease and is an independent risk factor for atherosclerosis. In this review, we examine the mechanisms by which IL-6 signals and its myriad effects in cardiovascular tissues that modulate the manifestations of vascular inflammation.