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Involvement of EP2 and EP4 Receptors in Eosinophilic Esophagitis: A Pilot Study. | LitMetric

Involvement of EP2 and EP4 Receptors in Eosinophilic Esophagitis: A Pilot Study.

Dig Dis Sci

Otto Loewi Research Center, Divison of Pharmacology, Medical University of Graz, Universitätsplatz 4, 8010, Graz, Austria.

Published: October 2019

AI Article Synopsis

  • The study explores the role of various prostaglandin receptors (DP2, EP1-EP4) in eosinophilic esophagitis (EoE) by analyzing their expression in blood eosinophils and esophageal tissue samples from patients.
  • Researchers found that EP2 and EP4 receptor expression was lower in EoE patients, whereas activation of these receptors reduced eosinophil adhesion and migration to the esophagus.
  • The findings suggest that while EP2 and EP4 may help regulate eosinophil activity, their activation could compromise the integrity of the esophageal barrier, implying a complex role in EoE pathology.

Article Abstract

Background: The prostaglandin D 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 PGE (EP1-EP4) and PGD (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 PGE and PGD 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744386PMC
http://dx.doi.org/10.1007/s10620-019-05623-5DOI Listing

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