title: Nasal administration of interleukin-33 induces airways angiogenesis and expression of multiple angiogenic factors in a murine asthma surrogate.
abstract: The T-helper cell type 2-promoting cytokine interleukin-33 (IL-33) has been implicated in asthma pathogenesis. Angiogenesis is a feature of airways remodelling in asthma. We hypothesized that IL-33 induces airways angiogenesis and expression of angiogenic factors in an established murine surrogate of asthma. In the present study, BALB/c mice were subjected to serial intranasal challenge with IL-33 alone for up to 70 days. In parallel, ovalbumin (OVA) -sensitized mice were subjected to serial intranasal challenge with OVA or normal saline to serve as positive and negative controls, respectively. Immunohistochemical analysis of expression of von Willebrand factor and erythroblast transformation-specific-related gene, both blood vessel markers, and angiogenic factors angiogenin, insulin-like growth factor-1, endothelin-1, epidermal growth factor and amphiregulin was performed in lung sections ex vivo. An established in-house assay was used to test whether IL-33 was able to induce microvessel formation by human vascular endothelial cells. Results showed that serial intranasal challenge of mice with IL-33 or OVA resulted in proliferation of peribronchial von Willebrand factor-positive blood vessels to a degree closely related to the total expression of the angiogenic factors amphiregulin, angiogenin, endothelin-1, epidermal growth factor and insulin-like growth factor-1. IL-33 also induced microvessel formation by human endothelial cells in a concentration-dependent fashion in vitro. Our data are consistent with the hypothesis that IL-33 has the capacity to induce angiogenesis at least partly by increasing local expression of multiple angiogenic factors in an allergen-independent murine asthma surrogate, and consequently that IL-33 or its receptor is a potential novel molecular target for asthma therapy.
authors.affiliation: The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shan
authors.affiliation: The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Department of Laboratory Animal Sciences, Capital Medical University, Beijing, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lv
authors.affiliation: The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Yi
authors.affiliation: The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Division of Asthma, Allergy & Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Corrigan
authors.affiliation: The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Quangeng
authors.affiliation: The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.|Division of Asthma, Allergy & Lung Biology, MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, UK.
authors.forename: Sun
authors.initials: S
authors.lastname: Ying
mesh_terms: D000281:Administration, Intranasal; D043925:Angiogenesis Inducing Agents / Q000032:analysis*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D004815:Epidermal Growth Factor / Q000032:analysis; D005260:Female; D000067596:Interleukin-33 / Q000008:administration & dosage* / Q000494:pharmacology; D008168:Lung / Q000098:blood supply*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects*
chemical_list: D043925:Angiogenesis Inducing Agents; D000067596:Interleukin-33; D004815:Epidermal Growth Factor
keywords: angiogenesis; asthma; interleukin-33; murine model