Angiopoietin-1 Protects against Airway Inflammation and Hyperreactivity in Asthma

Camargo Madeira Simoes, Davina, Vassilakopoulos, Theodoros, Toumpanakis, Dimitrios, Petrochilou, Kalomira, Roussos, Charis and Papapetropoulos, Andreas (2008) Angiopoietin-1 Protects against Airway Inflammation and Hyperreactivity in Asthma. American Journal of Respiratory and Critical Care Medicine, 177 (12). pp. 1314-1321. ISSN 1073-449X

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Abstract

Rationale: The angiopoietins (Ang) comprise a family of growth factors mainly known for their role in blood vessel formation and remodeling. The best-studied member, Ang-1, exhibits antiapoptotic and antiinflammatory effects. Although the involvement of Ang-1 in angiogenesis is well recognized, little information exists about its role in respiratory physiology and disease. On the basis of its ability to inhibit vascular permeability, adhesion molecule expression, and cytokine production, we hypothesized that Ang-1 administration might exert a protective role in asthma.

Objectives: To determine changes in the expression of Ang and to assess the ability of Ang-1 to prevent the histologic, biochemical, and functional changes observed in an animal model of asthma.

Methods: To test our hypothesis, a model of allergic airway disease that develops after ovalbumin (OVA) sensitization and challenge was used.

Measurements and Main Results: Ang-1 expression was reduced at the mRNA and protein levels in lung tissue of mice sensitized and challenged with OVA, leading to reduced Tie2 phosphorylation. Intranasal Ang-1 treatment prevented the OVA-induced eosinophilic lung infiltration, attenuated the increase in IL-5 and IL-13, and reduced eotaxin and vascular cell adhesion molecule 1 expression. These antiinflammatory actions of Ang-1 coincided with higher levels of IκB and decreased nuclear factor-κB binding activity. More importantly, Ang-1 reversed the OVA-induced increase in tissue resistance and elastance, improving lung function.

Conclusions: We conclude that Ang-1 levels are decreased in asthma and that administration of Ang-1 might be of therapeutic value because it prevents the increased responsiveness of the airways to constrictors and ameliorates inflammation.

Item Type:	Article
Uncontrolled Keywords:	airway resistance, interleukin 5, eotaxin, VCAM-1, nuclear factor-κB
Subjects:	B100 Anatomy, Physiology and Pathology
Department:	Faculties > Health and Life Sciences > Sport, Exercise and Rehabilitation
Depositing User:	Becky Skoyles
Date Deposited:	15 Dec 2017 11:43
Last Modified:	12 Oct 2019 11:48
URI:	http://nrl.northumbria.ac.uk/id/eprint/32868

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