An endothelial microRNA-1-regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis.
An endothelial microRNA-1-regulated network controls eosinophil trafficking in asthma and chronic rhinosinusitis.
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DOI：
10.1016/j.jaci.2019.10.031
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发表时间：
2020-03
期刊：
影响因子：
--
通讯作者：
Takyar SS
中科院分区：
文献类型：
--
作者：
Korde A;Ahangari F;Haslip M;Zhang X;Liu Q;Cohn L;Gomez JL;Chupp G;Pober JS;Gonzalez A;Takyar SS
气道嗜酸性粒细胞增多是哮喘和慢性鼻窦炎（CRS）的一个突出特征，内皮细胞在嗜酸性粒细胞运输中发挥着关键作用。迄今为止，microRNA-1 (miR-1) 是唯一已知在哮喘模型的肺内皮细胞中受到调节的 microRNA。我们试图确定内皮 miR-1 在过敏性气道炎症中的作用。我们使用定量 RT-PCR 测量了 microRNA 和 mRNA 表达。我们使用卵清蛋白和屋尘螨哮喘模型。 miR-1 的内皮特异性过表达是通过慢病毒载体递送或转基因诱导实现的。通过使用刚果红和抗嗜酸性粒细胞过氧化物酶染色来定量组织嗜酸性粒细胞增多。我们用赛克斯-摩尔粘附室测量了嗜酸性粒细胞的结合。通过使用抗 Argonaute2 RNA 免疫沉淀来评估 RNA 诱导的沉默复合物的靶标募集。使用流式细胞术测量表面P-选择素水平。血清miR-1水平与哮喘患者的痰液嗜酸性粒细胞增多、气道阻塞和住院次数以及CRS患者的鼻窦组织嗜酸性粒细胞增多呈负相关。 IL-13 刺激降低了人肺内皮细胞中 miR-1 的水平。内皮特异性的 miR-1 过度表达可减少小鼠模型中的气道嗜酸性粒细胞增多和哮喘表型，并抑制 IL-13 诱导的嗜酸性粒细胞与内皮细胞的结合。 miR-1 将 P-选择素、胸腺基质淋巴细胞生成素、eotaxin-3 和血小板生成素受体招募到 RNA 诱导的沉默复合物中；下调肺内皮细胞中的这些基因； IL-13 刺激的内皮细胞表面 P-选择素水平降低。在我们的哮喘和 CRS 队列中，miR-1 水平与其靶基因呈负相关。内皮 miR-1 在过敏性气道炎症中调节嗜酸性粒细胞运输。 miR-1 对哮喘患者和 CRS 患者具有治疗潜力。
Airway eosinophilia is a prominent feature of asthma and chronic rhinosinusitis (CRS), and the endothelium plays a key role in eosinophil trafficking. To date, microRNA-1 (miR-1) is the only microRNA known to be regulated in the lung endothelium in asthma models. We sought to determine the role of endothelial miR-1 in allergic airway inflammation. We measured microRNA and mRNA expression using quantitative RT-PCR. We used ovalbumin and house dust mite models of asthma. Endothelium-specific overexpression of miR-1 was achieved through lentiviral vector delivery or induction of a transgene. Tissue eosinophilia was quantified by using Congo red and anti-eosinophil peroxidase staining. We measured eosinophil binding with a Sykes-Moore adhesion chamber. Target recruitment to RNA-induced silencing complex was assessed by using anti-Argonaute2 RNA immunoprecipitation. Surface P-selectin levels were measured by using flow cytometry. Serum miR-1 levels had inverse correlations with sputum eosinophilia, airway obstruction, and number of hospitalizations in asthmatic patients and sinonasal tissue eosinophilia in patients with CRS. IL-13 stimulation decreased miR-1 levels in human lung endothelium. Endothelium-specific overexpression of miR-1 reduced airway eosinophilia and asthma phenotypes in murine models and inhibited IL-13–induced eosinophil binding to endothelial cells. miR-1 recruited P-selectin, thymic stromal lymphopoietin, eotaxin-3, and thrombopoietin receptor to the RNA-induced silencing complex; downregulated these genes in the lung endothelium; and reduced surface P-selectin levels in IL-13–stimulated endothelial cells. In our asthma and CRS cohorts, miR-1 levels correlated inversely with its target genes. Endothelial miR-1 regulates eosinophil trafficking in the setting of allergic airway inflammation. miR-1 has therapeutic potential in asthmatic patients and patients with CRS.
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DOI：
10.1084/jem.20062211
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allakhverdi Z;Comeau MR;Jessup HK;Yoon BR;Brewer A;Chartier S;Paquette N;Ziegler SF;Sarfati M;Delespesse G
通讯作者：
Delespesse G
DOI：
10.1073/pnas.061307098
发表时间：
2001-03-27
影响因子：
11.1
作者：
Denis, CV;André, P;Wagner, DD
通讯作者：
Wagner, DD
影响因子：
4.6
作者：
Bartel S;Schulz N;Alessandrini F;Schamberger AC;Pagel P;Theis FJ;Milger K;Noessner E;Stick SM;Kicic A;Eickelberg O;Freishtat RJ;Krauss-Etschmann S
通讯作者：
Krauss-Etschmann S
DOI：
10.4049/jimmunol.182.2.1119
发表时间：
2009-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Barrett NA;Maekawa A;Rahman OM;Austen KF;Kanaoka Y
通讯作者：
Kanaoka Y
影响因子：
158.5
作者：
Chupp, Geoffrey L.;Lee, Chun Geun;Elias, Jack A.
通讯作者：
Elias, Jack A.