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 periph...

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Publicado en:Digestive Diseases & Sciences Vol. 64; no. 10; pp. 2806 - 2815
Autores principales: Durchschein, Franziska, Eherer, Andreas, Grill, Magdalena, Sturm, Eva M., Pommer, Veronika, Langner, Cord, Högenauer, Christoph, Schicho, Rudolf
Formato: research Journal Article
Publicado: Springer Nature Oct2019
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Oct2019
      vid: 64
      iid: 10
      pid: 237
      pub: Springer Nature
      place: New York, New York
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        10.1007/s10620-019-05623-5
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        atl: Involvement of EP2 and EP4 Receptors in Eosinophilic Esophagitis: A Pilot Study.
      aug:
        au:
          Durchschein, Franziska
          Eherer, Andreas
          Grill, Magdalena
          Sturm, Eva M.
          Pommer, Veronika
          Langner, Cord
          Högenauer, Christoph
          Schicho, Rudolf
        affil: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
      sug:
        subj:
          Receptors, Cell Surface Analysis
          Eosinophilic Esophagitis Pathology
          Eosinophils Drug Effects
          Receptors, Cell Surface
          Eosinophils Metabolism
          Eosinophilic Esophagitis Metabolism
          Eosinophilic Esophagitis Blood
          Prostaglandins, Synthetic Pharmacodynamics
          Vasodilator Agents Analogs and Derivatives
          Human
          Vasodilator Agents Pharmacodynamics
          Immunohistochemistry
          Cell Physiology
          Ethers Pharmacodynamics
          Pilot Studies
          Cells, Cultured
          Cell Migration Assays Methods
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Arthritis Impact Measurement Scales
          Funding Source
      ab: 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.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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