Role of Ep2 and Ep4 receptors in airway microvascular leak induced by prostaglandin E2

Jones, Victoria, Birrell, Mark, Maher, Sarah, Griffiths, Mark, Grace, Megan, O'Donnell, Valerie Bridget ORCID: https://orcid.org/0000-0003-4089-8460, Clark, Stephen Robert ORCID: https://orcid.org/0000-0001-5907-9671 and Belisi, Maria 2016. Role of Ep2 and Ep4 receptors in airway microvascular leak induced by prostaglandin E2. British Journal of Pharmacology 173 (6) , pp. 992-1004. 10.1111/bph.13400

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Abstract

Background and Purpose Airway microvascular leak (MVL) involves the extravasation of proteins from post-capillary venules into surrounding tissue. MVL is a cardinal sign of inflammation and an important feature of airway inflammatory diseases such as asthma. Prostaglandin E2 (PGE2), a product of cyclooxygenase mediated metabolism of arachidonic acid, binds to 4 receptors, termed EP1-4. PGE2 has a wide variety of effects within the airway, including modulation of inflammation, sensory nerve activation and airway tone. However, the effect of PGE2 on airway MVL and the receptor/s that mediate this have not been described. Experimental Approach Evans Blue dye was used as a marker of airway MVL and selective EP receptor agonists and antagonists were used alongside EP receptor deficient mice to define the receptor subtype involved. Key Results PGE2 induced significant airway MVL in mice and guinea pigs. A significant reduction in PGE2-induced MVL was demonstrated in Ptger2-/- and Ptger4-/- mice and in wild type mice pre-treated simultaneously with EP2 (PF-04418948) and the EP4 (ER-819762) receptor antagonists. In a model of allergic asthma, an increase in airway levels of PGE2 was associated with a rise in MVL; this change was absent in Ptger2-/- and Ptger4-/- mice. Conclusions and Implications PGE2 is a key mediator produced by the lung and has widespread effects according to the EP receptor activated. Airway MVL represents a response to injury and under ‘disease’ conditions is a prominent feature of airway inflammation. The data presented highlight a key role for EP2 and EP4 receptors in MVL induced by PGE2. This article is protected by copyright. All rights reserved.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Publisher:	Wiley-Blackwell
ISSN:	0007-1188
Funders:	MRC
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	30 November 2015
Last Modified:	13 Nov 2024 16:00
URI:	https://orca.cardiff.ac.uk/id/eprint/85177

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