Identification of cardiac myocytes as the target of interleukin 11, a cardioprotective cytokine
Identification of cardiac myocytes as the target of interleukin 11, a cardioprotective cytokine
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DOI：
10.1016/j.cyto.2007.05.011
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发表时间：
2007-05-01
期刊：
影响因子：
3.8
通讯作者：
Azuma, Junichi
中科院分区：
文献类型：
--
作者：
Kimura, Ryusuke;Maeda, Makiko;Azuma, Junichi
白细胞介素（IL）-6家族细胞因子与糖蛋白130（gp 130）共同作为信号转导受体组分，在维持心脏稳态中起重要作用。IL-11是IL-6家族细胞因子的一员，在心肌细胞中表达，但IL-11在心脏中的功能仍有待阐明。在本研究中，首先，我们表明IL-11给药减少了心脏的缺血/再灌注损伤。IL-11受体alp在心肌细胞中表达。IL-11处理迅速激活心肌细胞中的信号转导和转录激活因子3（STAT 3）和细胞外信号调节激酶（ERK）1/2。IL-11刺激导致磷酸化STAT 3移位到细胞核中。免疫荧光显微镜分析显示，IL-11处理导致细胞伸长，与IL-6家族的其他心肌营养成员如白血病抑制因子的情况一样。最后，我们表明，IL-11治疗赋予了对过氧化氢诱导的细胞死亡的抵抗力，这被显性负性STAT 3的腺病毒转移所消除，但不被U 0126对ERK 1/2的抑制所消除。这些发现表明IL-11介导心肌细胞中的细胞保护信号，表明IL-11具有表现出心脏保护作为一种新的生物学功能的潜力。(c)2007爱思唯尔有限公司保留所有权利。
Interleukin (IL)-6 family cytokines, which share glycoprotein 130 (gp 130) as a signal-transducing receptor component, play important roles in the maintenance of cardiac homeostasis. IL-11, a member of IL-6 family cytokines, is expressed in cardiac myocytes, though it remains to be elucidated how IL-11 functions in the hearts. In the present study, first, we showed that IL-11 administration reduced the ischemia/reperfusion injury in the hearts. IL-11 receptor alp was expressed in cardiomyocytes. IL-11 treatment rapidly activated signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) 1/2 in cardiac myocytes. IL-11 stimulation resulted in the translocation of phosphorylated STAT3 into nuclei. Immunofluorescence microscopic analyses revealed that IL-11 treatment led to the cell elongation, as is the case with other cardiotrophic members of IL-6 family, such as leukemia inhibitory factor. Finally we showed that IL-11 treatment conferred the resistance to cell death induced by hydrogen peroxide, which was abrogated by adenoviral transfer of dominant negative STAT3, but not by the inhibition of ER K 1/2 with U0126. These findings indicate that IL-11 mediates cytoprotective signals in cardiomyocytes, proposing that IL-11 has the potential to exhibit cardioprotection as a novel biological function. (c) 2007 Elsevier Ltd. All rights reserved.