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Eur Respir J. 2016 Mar;47(3):769-82. doi: 10.1183/13993003.00437-2015. Epub 2016 Feb 11.

Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes.

Author information

1
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.
2
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.
3
Cellular Immunology Laboratory, Division of Cell Biology, Centre for Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
4
7th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital "Sotiria", Athens, Greece.
5
Medical Research Council and Asthma UK Centre for Mechanisms of Allergic Asthma, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK.
6
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.
7
Department of Asthma, Allergy and Respiratory Science, King's College London School of Medicine, London, UK.
8
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.
9
7th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital "Sotiria", Athens, Greece Both authors contributed equally.

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.

PMID:
26869672
DOI:
10.1183/13993003.00437-2015
[Indexed for MEDLINE]
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