Research

Activity of the cyclooxygenase 2-prostaglandin-E prostanoid receptor pathway in mice exposed to house dust mite aeroallergens, and impact of exogenous prostaglandin E₂

Aida Herrerias¹ , Rosa Torres^1,2,3 , Mariona Serra¹ , Alberto Marco⁴ , Laura Pujols^2,3 , César Picado^2,3 and Fernando de Mora¹

¹  Department of Pharmacology, Universitat Autònoma de Barcelona, Barcelona, Spain

²  Department of Pneumology and Respiratory Allergy, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Spain

³  CIBER [Centro de Investigación Biomédica en Red] de Enfermedades Respiratorias, Spain

⁴  Department of Animal Pathology, Universitat Autònoma de Barcelona, Barcelona, Spain

author email corresponding author email

Journal of Inflammation 2009, 6:30doi:10.1186/1476-9255-6-30

Published:	30 October 2009

Abstract

Background

Prostaglandin E₂ (PGE₂), experimentally administered to asthma patients or assayed in murine models, improves allergen-driven airway inflammation. The mechanisms are unknown, but fluctuations of the endogenous cyclooxygenase (COX)-2/prostaglandin/E prostanoid (EP) receptor pathway activity likely contribute to the clinical outcome. We analyzed the activity of the pathway in mice sensitized to aeroallergens, and then studied its modulation under exogenous PGE₂.

Methods

Mice were exposed to house dust mite (HDM) aeroallergens, a model that enable us to mimic the development of allergic asthma in humans, and were then treated with either subcutaneous PGE₂ or the selective EP1/3 receptor agonist sulprostone. Simultaneously with airway responsiveness and inflammation, lung COX-2 and EP receptor mRNA expression were assessed. Levels of PGE₂, PGI₂, PGD₂ were also determined in bronchoalveolar lavage fluid.

Results

HDM-induced airway hyperreactivity and inflammation were accompanied by increased COX-2 mRNA production. In parallel, airway PGE₂ and PGI₂, but not PGD₂, were upregulated, and the EP2 receptor showed overexpression. Subcutaneous PGE₂ attenuated aeroallergen-driven airway eosinophilic inflammation and reduced endogenous PGE₂ and PGI₂ production. Sulprostone had neither an effect on airway responsiveness or inflammation nor diminished allergen-induced COX-2 and PGE₂ overexpression. Finally, lung EP2 receptor levels remained high in mice treated with PGE₂, but not in those treated with sulprostone.

Conclusion

The lung COX-2/PGE₂/EP2 receptor pathway is upregulated in HDM-exposed mice, possibly as an effort to attenuate allergen-induced airway inflammation. Exogenous PGE₂ downregulates its endogenous counterpart but maintains EP2 overexpression, a phenomenon that might be required for administered PGE₂ to exert its protective effect.