title: IL-25 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma model.
abstract: BACKGROUND
  Th2-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.
  
  
  METHODS
  By 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.
  
  
  RESULTS
  Repetitive 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 angiogenesis in vitro.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China. yaoxiujuanhello@163.com.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China. wy_robin@ccmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University & Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China. liyanok@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China. 317144227@qq.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China. zqjy0405@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Animal Sciences, Capital Medical University, Beijing, People's Republic of China. wangjj@ccmu.edu.cn.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University & Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China. wenwang318@126.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China. lvzhe327@ccmu.edu.cn.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China. anyunq@ccmu.edu.cn.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: An
authors.affiliation: Dongfang Hospital, The Second Clinical Medical College of Beijing University of Chinese Medicine, Beijing, People's Republic of China. qindoctor@163.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Qin
authors.affiliation: King's College London, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Division of Asthma, Allergy & Lung Biology, London, UK. chris.corrigan@kcl.ac.uk.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Corrigan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University & Beijing Institute of Respiratory Medicine, Beijing, People's Republic of China. kewuhuang@126.com.
authors.forename: Kewu
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Respiratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, People's Republic of China. suny@ccmu.edu.cn.
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, People's Republic of China. ying.sun@kcl.ac.uk.|King's College London, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, Division of Asthma, Allergy & Lung Biology, London, UK. ying.sun@kcl.ac.uk.
authors.forename: Sun
authors.initials: S
authors.lastname: Ying
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D002908:Chronic Disease; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007378:Interleukins; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D010047:Ovalbumin; D011994:Recombinant Proteins; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D042501:Angiogenic Proteins; D007378:Interleukins; C442281:Mydgf protein, mouse; D011994:Recombinant Proteins; D010047:Ovalbumin