title: Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes.
abstract: Activin-A is a pleiotropic cytokine that regulates allergic inflammation. Its role in the regulation of angiogenesis, a key feature of airways remodelling in asthma, remains unexplored. Our objective was to investigate the expression of activin-A in asthma and its effects on angiogenesis in vitro.Expression of soluble/immunoreactive activin-A and its receptors was measured in serum, bronchoalveolar lavage fluid (BALF) and endobronchial biopsies from 16 healthy controls, 19 patients with mild/moderate asthma and 22 severely asthmatic patients. In vitro effects of activin-A on baseline and vascular endothelial growth factor (VEGF)-induced human endothelial cell angiogenesis, signalling and cytokine release were compared with BALF concentrations of these cytokines in vivo.Activin-A expression was significantly elevated in serum, BALF and bronchial tissue of the asthmatics, while expression of its protein receptors was reduced. In vitro, activin-A suppressed VEGF-induced endothelial cell proliferation and angiogenesis, inducing autocrine production of anti-angiogenic soluble VEGF receptor (R)1 and interleukin (IL)-18, while reducing production of pro-angiogenic VEGFR2 and IL-17. In parallel, BALF concentrations of soluble VEGFR1 and IL-18 were significantly reduced in severe asthmatics in vivo and inversely correlated with angiogenesis.Activin-A is overexpressed and has anti-angiogenic effects in vitro that are not propagated in vivo, where reduced basal expression of its receptors is observed particularly in severe asthma.
authors: Cellular Immunology Laboratory, Division of Cell Biology, Centre for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece 7th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital "Sotiria", Athens, Greece These authors contributed equally.
authors: Konstantinos
authors: K
authors: Samitas
authors: Cellular Immunology Laboratory, Division of Cell Biology, Centre for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece These authors contributed equally.
authors: Nikolaos
authors: N
authors: Poulos
authors: Cellular Immunology Laboratory, Division of Cell Biology, Centre for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece These authors contributed equally.
authors: Maria
authors: M
authors: Semitekolou
authors: Cellular Immunology Laboratory, Division of Cell Biology, Centre for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors: Ioannis
authors: I
authors: Morianos
authors: Cellular Immunology Laboratory, Division of Cell Biology, Centre for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors: Sofia
authors: S
authors: Tousa
authors: 7th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital "Sotiria", Athens, Greece.
authors: Erasmia
authors: E
authors: Economidou
authors: Medical Research Council and Asthma UK Centre for Mechanisms of Allergic Asthma, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK.
authors: Douglas S
authors: DS
authors: Robinson
authors: Medical Research Council and Asthma UK Centre for Mechanisms of Allergic Asthma, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK Department of Allergy and Medical Rhinology, Royal National Throat, Nose and Ear Hospital, University College, London, UK.
authors: Harsha H
authors: HH
authors: Kariyawasam
authors: 7th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital "Sotiria", Athens, Greece.
authors: Eleftherios
authors: E
authors: Zervas
authors: Department of Asthma, Allergy and Respiratory Science, King's College London School of Medicine, London, UK.
authors: Christopher J
authors: CJ
authors: Corrigan
authors: Department of Asthma, Allergy and Respiratory Science, King's College London School of Medicine, London, UK.
authors: Sun
authors: S
authors: Ying
authors: Cellular Immunology Laboratory, Division of Cell Biology, Centre for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece Both authors contributed equally gxanthou@bioacademy.gr.
authors: Georgina
authors: G
authors: Xanthou
authors: 7th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital "Sotiria", Athens, Greece Both authors contributed equally.
authors: Mina
authors: M
authors: Gaga
mesh_terms: D028341:Activins / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D020382:Interleukin-18; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C422405:activin A; D028341:Activins; D040262:Receptors, Vascular Endothelial Growth Factor