Interleukin-33 Induces Expression of Adhesion Molecules and Inflammatory Activation in Human Endothelial Cells and in Human Atherosclerotic Plaques
Interleukin-33 Induces Expression of Adhesion Molecules and Inflammatory Activation in Human Endothelial Cells and in Human Atherosclerotic Plaques
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DOI：
10.1161/atvbaha.111.231431
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发表时间：
2011-09-01
影响因子：
8.7
通讯作者：
Wojta, Johann
中科院分区：
文献类型：
--
作者：
Demyanets, Svitlana;Konya, Viktoria;Wojta, Johann
β-白细胞介素（IL）-33是最近描述的细胞因子IL-1家族的成员，并且它是ST 2受体的配体。虽然IL-33对免疫系统的影响已被广泛研究，但这种细胞因子在心血管系统中的性质却研究得少得多。方法/结果-我们在此表明，IL-33促进人白细胞与人内皮细胞单层的粘附，并显著增加血管细胞粘附分子-1，细胞间粘附分子-1，内皮选择素，以及体外人冠状动脉和人脐静脉内皮细胞中以及离体人动脉粥样硬化斑块中的单核细胞趋化蛋白-1蛋白产生和mRNA表达。ST 2融合蛋白，而不是IL-1受体拮抗剂，取消这些影响。IL-33诱导人冠状动脉内皮细胞和人脐静脉内皮细胞核因子-κ B p50和p65亚单位向细胞核的易位，以及人脐静脉内皮细胞中I κ B激酶2或I κ B α显性负性形式的过表达消除了IL-33诱导的粘附分子和单核细胞趋化蛋白-1 mRNA的表达。我们检测到IL-33和ST 2的蛋白质和mRNA水平在人颈动脉粥样硬化plaic. Conclusion，我们假设，IL-33可能有助于早期事件的内皮激活特征的发展动脉粥样硬化病变的血管壁，通过促进粘附分子和促炎细胞因子在内皮细胞的表达。（Arterioscler Thromb Vasc Biol.2011;31：2080-2089.）
Objective-Interleukin (IL)-33 is the most recently described member of the IL-1 family of cytokines and it is a ligand of the ST2 receptor. While the effects of IL-33 on the immune system have been extensively studied, the properties of this cytokine in the cardiovascular system are much less investigated.Methods/Results-We show here that IL-33 promoted the adhesion of human leukocytes to monolayers of human endothelial cells and robustly increased vascular cell adhesion molecule-1, intercellular adhesion molecule-1, endothelial selectin, and monocyte chemoattractant protein-1 protein production and mRNA expression in human coronary artery and human umbilical vein endothelial cells in vitro as well as in human explanted atherosclerotic plaques ex vivo. ST2-fusion protein, but not IL-1 receptor antagonist, abolished these effects. IL-33 induced translocation of nuclear factor-kappa B p50 and p65 subunits to the nucleus in human coronary artery endothelial cells and human umbilical vein endothelial cells and overexpression of dominant negative form of I kappa B kinase 2 or I kappa B alpha in human umbilical vein endothelial cells abolished IL-33-induced adhesion molecules and monocyte chemoattractant protein-1 mRNA expression. We detected IL-33 and ST2 on both protein and mRNA level in human carotid atherosclerotic plaques.Conclusion-We hypothesize that IL-33 may contribute to early events in endothelial activation characteristic for the development of atherosclerotic lesions in the vessel wall, by promoting adhesion molecules and proinflammatory cytokine expression in the endothelium. (Arterioscler Thromb Vasc Biol. 2011;31:2080-2089.)