Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4
Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4
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DOI：
10.1016/s0014-5793(03)00482-4
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发表时间：
2003-06-05
期刊：
影响因子：
3.5
通讯作者：
McElvaney, NG
中科院分区：
文献类型：
--
作者：
Devaney, JM;Greene, CM;McElvaney, NG
囊性纤维化在肺中的特征在于高水平的中性粒细胞弹性蛋白酶（NE）。NE通过IL-1受体相关激酶信号通路诱导白细胞介素-8（IL-8）表达。在这里，我们表明，这些事件涉及细胞表面膜结合的Toll样受体4（TLR 4）。我们证明，转染TLR 4 cDNA（REK-TLR 4）的人胚肾（HEK）293细胞表达TLR 4 mRNA和蛋白，并诱导IL-8启动子活性响应NE。用NE处理HEK-TLR 4和人支气管上皮细胞均降低TLR 4蛋白表达。此外，TLR 4中和抗体消除NE诱导的IL-8产生，并诱导对次级脂多糖刺激的耐受性。这些数据暗示TLR 4参与NE诱导的支气管上皮中IL-8的表达。(C)2003年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
Cystic fibrosis is characterised in the lungs by high levels of neutrophil elastase (NE). NE induces interleukin-8 (IL-8) expression via an IL-1 receptor-associated kinase signalling pathway. Here, we show that these events involve the cell surface membrane bound toll-like receptor 4 (TLR4). We demonstrate that human embryonic kidney (HEK)293 cells transfected with a TLR4 cDNA (REK-TLR4) express TLR4 mRNA and protein and induce IL-8 promoter activity in response to NE. Treatment of both HEK-TLR4 and human bronchial epithelial cells with NE decreases TLR4 protein expression. Furthermore, a TLR4 neutralising antibody abrogates NE-induced IL-8 production, and induces tolerance to a secondary lipopolysaccharide stimulus. These data implicate TLR4 in NE induced IL-8 expression in bronchial epithelium. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.