Interleukin-33/ST2 signaling promotes production of interleukin-6 and interleukin-8 in systemic inflammation in cigarette smoke-induced chronic obstructive pulmonary disease mice
Interleukin-33/ST2 signaling promotes production of interleukin-6 and interleukin-8 in systemic inflammation in cigarette smoke-induced chronic obstructive pulmonary disease mice
复制标题
白细胞介素 33/ST2 信号传导促进香烟烟雾诱发的慢性阻塞性肺病小鼠全身炎症中白细胞介素 6 和白细胞介素 8 的产生
DOI：
10.1016/j.bbrc.2014.05.073
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发表时间：
2014-07-18
影响因子：
3.1
通讯作者：
Xie, Jungang
中科院分区：
文献类型：
--
作者：
Wu, Hongxu;Yang, Shifang;Xie, Jungang
白细胞介素-33是白细胞介素-1家族的新成员。最近的研究表明，IL-33在香烟引起的慢性阻塞性肺疾病（COPD）小鼠的肺部增加，并在慢性气道炎症中起关键作用。为了研究IL-33在全身炎症中的作用，我们通过被动吸烟诱导COPD小鼠模型，检测IL-33在支气管内皮细胞和外周血单个核细胞（PBMCs）中的表达。分离后的PBMCs进行体外培养和刺激。我们测量了不同组pbmc中白细胞介素-6和白细胞介素-8的表达。IL-33在COPD小鼠支气管内皮细胞和支气管内皮细胞中高表达。在香烟烟雾提取物（CSE）刺激下，IL-33诱导和增强了IL-6和IL-8的表达。CSE和IL-33刺激COPD小鼠PBMCs产生更多的IL-6和IL-8。在IL-33和可溶性ST2共同刺激下，IL-6和IL-8的表达降低。IL-33刺激的PBMCs中ST2 mRNA的表达量增加。经多种MAPK抑制剂预处理后，除p38 MAPK抑制剂外，PBMCs中IL-6和IL-8的分泌均未减少。我们发现IL-33可以通过p38 MAPK通路诱导和增强COPD小鼠PBMCs中IL-6和IL-8的表达，是COPD小鼠全身性炎症生成IL-6和IL-8的启动子。(C) 2014爱思唯尔公司版权所有。
Interleukin-33 is a newly described member of the interleukin-1 family. Recent research suggests that IL-33 is increased in lungs and plays a critical role in chronic airway inflammation in cigarette smoke-induced chronic obstructive pulmonary disease (COPD) mice. To determine the role of IL-33 in systemic inflammation, we induced COPD mice models by passive cigarette smoking and identified the IL-33 expression in bronchial endothelial cells and peripheral blood mononuclear cells (PBMCs) of them. After isolation, PBMCs were cultured and stimulated in vitro. We measured expressions of interleukin-6 and interleukin-8 in PBMCs in different groups. The expression of IL-33 in bronchial endothelial cells and PBMCs of COPD mice were highly expressed. Stimulated by cigarette smoke extract (CSE), the expression of IL-6 and IL-8 were induced and enhanced by IL-33. PBMCs of COPD mice produced more IL-6 and IL-8 stimulated by CSE and IL-33. Expression of IL-6 and IL-8 were decreased when stimulated by IL-33 together with soluble ST2. The mRNA production of ST2 in IL-33 stimulated PBMCs was increased. Being pretreated with several kinds of MAPK inhibitors, the secretions of IL-6 and IL-8 in PBMCs did not decrease except for the p38 MAPK inhibitor. We found that IL-33 could induce and enhance the expression of IL-6 and IL-8 in PBMCs of COPD mice via p38 MAPK pathway, and it is a promoter of the IL-6 and IL-8 production in systemic inflammation in COPD mice. (C) 2014 Elsevier Inc. All rights reserved.