Activation of the Prostaglandin E2 receptor EP2 prevents house dust mite-induced airway hyperresponsiveness and inflammation by restraining mast cells' activity.
Clin Exp Allergy
; 45(10): 1590-600, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-25823713
ABSTRACT
BACKGROUND:
Prostaglandin E2 (PGE2 ) has been proposed to exert antiasthmatic effects in patients, to prevent antigen-induced airway pathology in murine models, and to inhibit mast cells (MC) activity in vitro.OBJECTIVE:
To assess in a murine model whether the protective effect of PGE2 may be a consequence of its ability to activate the E-prostanoid (EP)2 receptor on airway MC.METHODS:
Either BALB/c or C57BL/6 mice were exposed intranasally (i.n.) to house dust mite (HDM) aeroallergens. Both strains were given PGE2 locally (0.3 mg/kg), but only BALB/c mice were administered butaprost (EP2 agonist 0.3 mg/kg), or AH6809 (EP2 antagonist; 2.5 mg/kg) combined with the MC stabilizer sodium cromoglycate (SCG 25 mg/kg). Airway hyperresponsiveness (AHR) and inflammation, along with lung MC activity, were evaluated. In addition, butaprost's effect was assessed in MC-mediated passive cutaneous anaphylaxis (PCA) in mice challenged with 2,4-dinitrophenol (DNP).RESULTS:
Selective EP2 agonism attenuated aeroallergen-caused AHR and inflammation in HDM-exposed BALB/c mice, and this correlated with a reduced lung MC activity. Accordingly, the blockade of endogenous PGE2 by means of AH6809 worsened airway responsiveness in sensitive BALB/c mice, and such worsening was reversed by SCG. The relevance of MC to PGE2 -EP2 driven protection was further highlighted in MC-dependent PCA, where butaprost fully prevented MC-induced ear swelling. Unlike in BALB/c mice, PGE2 did not protect the airways of HDM-sensitized C57BL/6 animals, a strain in which we showed MC to be irrelevant to aeroallergen-driven AHR and inflammation. CONCLUSIONS & CLINICAL RELEVANCE The beneficial effect of both exogenous and endogenous PGE2 in aeroallergen-sensitized mice may be attributable to the activation of the EP2 receptor, which in turn acts as a restrainer of airway MC activity. This opens a path towards the identification of therapeutic targets against asthma along the 'EP2 -MC-airway' axis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Asma
/
Dinoprostona
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Pyroglyphidae
/
Subtipo EP2 de Receptores de Prostaglandina E
/
Mastocitos
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
España