Activity of the cyclooxygenase 2-prostaglandin-E prostanoid receptor pathway in mice exposed to house dust mite aeroallergens, and impact of exogenous prostaglandin E
Herrerias, Aida (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Torres Blanch, Rosa (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Serra, Mariona (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)
Marco, Alberto (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Pujols, Laura (Hospital Clínic i Provincial de Barcelona)
Picado, César (Hospital Clínic i Provincial de Barcelona)
Mora Pérez, Fernando de (Universitat Autònoma de Barcelona. Departament de Farmacologia, de Terapèutica i de Toxicologia)

Data:	2009
Resum:	Prostaglandin E(PGE), 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 PGE. 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 PGEor 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 PGE, PGI, PGDwere also determined in bronchoalveolar lavage fluid. HDM-induced airway hyperreactivity and inflammation were accompanied by increased COX-2 mRNA production. In parallel, airway PGEand PGI, but not PGD, were upregulated, and the EP2 receptor showed overexpression. Subcutaneous PGEattenuated aeroallergen-driven airway eosinophilic inflammation and reduced endogenous PGEand PGIproduction. Sulprostone had neither an effect on airway responsiveness or inflammation nor diminished allergen-induced COX-2 and PGEoverexpression. Finally, lung EP2 receptor levels remained high in mice treated with PGE, but not in those treated with sulprostone. The lung COX-2/PGE/EP2 receptor pathway is upregulated in HDM-exposed mice, possibly as an effort to attenuate allergen-induced airway inflammation. Exogenous PGEdownregulates its endogenous counterpart but maintains EP2 overexpression, a phenomenon that might be required for administered PGEto exert its protective effect.
Ajuts:	Instituto de Salud Carlos III FIS/PI060592
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Journal of Inflammation (London, England), Vol. 6 (october 2009) , p. 30, ISSN 1476-9255

DOI: 10.1186/1476-9255-6-30
PMID: 19878559

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