Involvement of EP2 and EP4 Receptors in Eosinophilic Esophagitis: A Pilot Study.
BACKGROUND
The prostaglandin D2 receptor DP2 has been implicated in eosinophil infiltration and the development of eosinophilic esophagitis (EoE).


AIMS AND METHODS
In this study, we investigated an involvement of PGE2 (EP1-EP4) and PGD2 (DP1) receptors in EoE by measuring their expression in peripheral blood eosinophils and esophageal mucosal biopsies of EoE patients and by performing migration and adhesion assays with eosinophils from healthy donors.


RESULTS
Expression of EP2 and EP4, but not EP1 and EP3, was decreased in blood eosinophils of patients with EoE vs. control subjects. Adhesion of eosinophils to esophageal epithelial cells was decreased by EP2 receptor agonist butaprost and EP4 agonist ONO-AE1-329, whereas DP1 agonist BW245C increased adhesion. In chemotaxis assays with supernatant from human esophageal epithelial cells, only ONO-AE1-329 but not butaprost or BW245C inhibited the migration of eosinophils. Expression of EP and DP receptors in epithelial cells and eosinophils was detected in sections of esophageal biopsies from EoE patients by immunohistochemistry. qPCR of biopsies from EoE patients revealed that gene expression of EP4 and DP1 was the highest among PGE2 and PGD2 receptors. Esophageal epithelial cells in culture showed high gene expression for EP2 and EP4. Activation of EP2 and EP4 receptors decreased barrier integrity of esophageal epithelial cells in impedance assays.


CONCLUSIONS
Activation of EP2 and EP4 receptors may inhibit eosinophil recruitment to the esophageal mucosa. However, their activation could negatively affect esophageal barrier integrity suggesting that eosinophilic rather than epithelial EP2 and EP4 have a protective role in EoE.
['Durchschein|Franziska|F|', 'Eherer|Andreas|A|', 'Grill|Magdalena|M|', 'Sturm|Eva M|EM|', 'Pommer|Veronika|V|', 'Langner|Cord|C|', 'Högenauer|Christoph|C|', 'Schicho|Rudolf|R|0000-0002-5726-4731']
D000527:Alprostadil D002448:Cell Adhesion D054443:Cell Migration Assays D002478:Cells, Cultured D057765:Eosinophilic Esophagitis D004804:Eosinophils D000071041:Esophageal Mucosa D006801:Humans D007150:Immunohistochemistry D008738:Methyl Ethers D010865:Pilot Projects D011459:Prostaglandins E, Synthetic D058307:Receptors, Prostaglandin E, EP2 Subtype D058309:Receptors, Prostaglandin E, EP4 Subtype
Eosinophils DP1 Esophageal epithelial cells EP receptors Prostaglandin receptors