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Activation of the Prostaglandin E2 receptor EP 2 prevents house dust mite‐induced airway hyperresponsiveness and inflammation by restraining mast cells’ activity
Author(s) -
SerraPages M.,
Torres R.,
Plaza J.,
Herrerias A.,
CostaFarré C.,
Marco A.,
Jiménez M.,
Maurer M.,
Picado C.,
Mora F.
Publication year - 2015
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12542
Subject(s) - house dust mite , prostaglandin e2 receptor , prostaglandin e2 , immunology , pharmacology , prostaglandin d2 , inflammation , allergic inflammation , sensitization , chemistry , receptor , mast cell , agonist , bronchial hyperresponsiveness , medicine , allergy , endocrinology , lung , allergen , respiratory disease
Summary Background Prostaglandin E 2 ( PGE 2 ) 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 PGE 2 may be a consequence of its ability to activate the E‐prostanoid ( EP ) 2 receptor on airway MC . Methods Either BALB/c or C57 BL /6 mice were exposed intranasally (i.n.) to house dust mite ( HDM ) aeroallergens. Both strains were given PGE 2 locally (0.3 mg/kg), but only BALB/c mice were administered butaprost ( EP 2 agonist: 0.3 mg/kg), or AH 6809 ( EP 2 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 EP 2 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 PGE 2 by means of AH 6809 worsened airway responsiveness in sensitive BALB /c mice, and such worsening was reversed by SCG . The relevance of MC to PGE 2 ‐ EP 2 driven protection was further highlighted in MC ‐dependent PCA , where butaprost fully prevented MC ‐induced ear swelling. Unlike in BALB /c mice, PGE 2 did not protect the airways of HDM ‐sensitized C57 BL /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 PGE 2 in aeroallergen‐sensitized mice may be attributable to the activation of the EP 2 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 ‘ EP 2 ‐ MC ‐airway’ axis.