IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model.
IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model.
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IL-25 在小鼠哮喘模型中诱导气道血管生成和多种血管生成因子的表达
DOI：
10.1186/s12931-015-0197-3
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发表时间：
2015-03-18
影响因子：
5.8
通讯作者：
Ying S
中科院分区：
文献类型：
--
作者：
Yao X;Wang W;Li Y;Huang P;Zhang Q;Wang J;Wang W;Lv Z;An Y;Qin J;Corrigan CJ;Huang K;Sun Y;Ying S
研究背景促Th 2细胞因子IL-25可能通过其受体参与哮喘小鼠支气管黏膜血管重塑，该受体由血管内皮细胞和血管平滑肌细胞表达。方法采用IL-25诱导小鼠慢性哮喘模型，观察IL-25对血管生成、血管重塑和血管生成因子表达的影响，与经典的卵清蛋白（OVA）诱导的小鼠哮喘模型的变化进行了比较。将IL-25和OVA鼻内滴注到BALB/c小鼠的气道中长达55天。采用免疫组化或酶联免疫吸附试验（ELISA）检测肺组织切片、肺组织匀浆和支气管肺泡灌洗液中血管生成因子（vWF、angiogenin、endothelin-1、ERG、bFGF、EGF、IGF-1和VEGF）的含量。结果在OVA-预致敏的动物中，单独用IL-25或单独用OVA反复鼻内激发显著增加了小鼠气道中支气管周围vWF+血管，这与双调蛋白、血管生成素、内皮素-1、bFGF、EGF、IGF-1、VEGF和ERG。IL-25，但不是Th-2-细胞因子诱导的人angiogenesisin vitro.ConclusionsThe数据表明，慢性暴露的小鼠气道IL-25单独是能够重现局部血管生成的环境。因此，阻断IL-25可以减弱血管重塑并改善哮喘患者的预后。
BackgroundTh2-promoting cytokine IL-25 might contribute to bronchial mucosal vascular remodelling in asthma through its receptor expressed by vascular endothelial and vascular smooth muscle cells.MethodsBy utilising a newly established chronic asthma murine model induced by direct exposure of the airways to IL-25 alone, we examined effects of IL-25 on angiogenesis, vascular remodelling and expression of angiogenic factors, compared changes with those in a “classical” ovalbumin (OVA)-induced murine asthma model. IL-25 and OVA were intranasally instilled into the airways of BALB/c mice for up to 55 days. Airways vessels and angiogenic factors, including Von Willebrand Factor (vWF), amphiregulin, angiogenin, endothelin-1, transcription factor ERG, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor (IGF-1) and vascular endothelial growth factor (VEGF) in lung sections, homogenates and BAL fluid were detected and quantified by immunostaining or enzyme linked immunosorbent assay (ELISA). An in house assay was also utilised to compare the effects of IL-25 and other Th2-cytokines on angiogenesis by human vascular endothelial cells.ResultsRepetitive intranasal challenge with IL-25 alone or OVA alone in OVA-presensitised animals significantly increased peribronchial vWF+vessels in the murine airways, which was associated with remarkably elevated expression of amphiregulin, angiogenin, endothelin-1, bFGF, EGF, IGF-1, VEGF and ERG. IL-25, but not Th-2-cytokines induced human angiogenesisin vitro.ConclusionsThe data suggest that chronic exposure of murine airways to IL-25 alone is able to reproduce a local angiogenic milieu. Thus, blocking IL-25 may attenuate vascular remodelling and improve outcomes in asthma patients.
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DOI：
10.1111/j.1365-2222.2004.01895.x
发表时间：
2004-03
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
McMillan SJ;Lloyd CM
通讯作者：
Lloyd CM
影响因子：
14.2
作者：
Corrigan, Chris J.;Wang, Wei;Ying, Sun
通讯作者：
Ying, Sun
DOI：
10.1164/rccm.200207-710oc
发表时间：
2003-03-01
影响因子：
24.7
作者：
Chetta, A;Zanini, A;Olivieri, D
通讯作者：
Olivieri, D
DOI：
10.1073/pnas.1014241108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Corrigan, Chris J.;Wang, Wei;Ying, Sun
通讯作者：
Ying, Sun
影响因子：
4.4
作者：
Pan, GH;French, D;Gurney, AL
通讯作者：
Gurney, AL