β-adrenergic stimulation induces interleukin-18 expression via β2-AR, PI3K, Akt, IKK, and NF-κB
β-adrenergic stimulation induces interleukin-18 expression via β2-AR, PI3K, Akt, IKK, and NF-κB
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DOI：
10.1016/j.bbrc.2004.04.185
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发表时间：
2004-06-25
影响因子：
3.1
通讯作者：
Murray, DR
中科院分区：
文献类型：
--
作者：
Chandrasekar, B;Marelli-Berg, FM;Murray, DR
我们研究了β-肾上腺素能受体(β-AR)刺激是否通过激活核因子(NF)-kappaB在心肌和心源性内皮细胞(CDEC)中诱导了促炎细胞因子IL-18的表达。我们的结果表明，异丙肾上腺素(ISO)激活了核因子-kappaB DNA结合活性，并通过β(2)-AR信号诱导心肌和全身IL-18的分泌。此外，在CDEC中，ISO可增强基础启动子和诱导型启动子活性，增强IL-18基因转录和mRNA稳定性，并通过β(2)-AR激动剂诱导IL-18表达。信号需要G(I)、PI3K、Akt、IKK和NF-kappaB。总之，我们的结果首次表明，异丙肾上腺素通过β(2)-AR和核因子-kappaB依赖的机制诱导心肌和全身IL-18的分泌。类似的事件可能发生在心力衰竭中，这是一种以持续的β-AR激活为特征的疾病状态。(C)2004 Elsevier Inc.保留所有权利。
We investigated whether beta-adrenergic receptor (beta-AR) stimulation induces the expression of interleukin (IL)-18, a proinflammatory cytokine, in myocardium and in cardiac-derived endothelial cells (CDEC) via activation of nuclear factor (NF)-kappaB. Our results indicate that isoproterenol (ISO) activates NF-kappaB DNA binding activity, and induces myocardial and systemic elaboration of IL-18 via beta(2)-AR signaling. Furthermore, in CDEC, ISO increased basal and inducible promoter activities, increased IL-18 gene transcription and mRNA stability, and induced IL-18 expression via beta(2)-AR agonism. Signaling required G(i), PI3K, Akt, IKK, and NF-kappaB. In conclusion, our results indicate for the first time that isoproterenol induces myocardial and systemic elaboration of IL-18 via a beta(2)-AR and NF-kappaB-dependent mechanism. Similar events may occur in heart failure, a disease state characterized by sustained beta-AR activation. (C) 2004 Elsevier Inc. All rights reserved.