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.

中文翻译：

---

EP2和EP4受体在嗜酸性食管炎中的作用：一项初步研究。

背景技术前列腺素D 2受体DP 2已经涉及嗜酸性粒细胞浸润和嗜酸性食管炎（EoE）的发展。目的和方法在这项研究中，我们通过测量EoE患者外周血嗜酸性粒细胞和食管粘膜活检组织中PGE2（EP1-EP4）和PGD2（DP1）受体的表达，并通过嗜酸性粒细胞进行迁移和粘附试验，研究了它们在EoE中的参与来自健康的捐助者。结果与对照组相比，EoE患者血液嗜酸性粒细胞中EP2和EP4的表达降低，但EP1和EP3没有降低。EP2受体激动剂Butaprost和EP4激动剂ONO-AE1-329降低了嗜酸性粒细胞对食管上皮细胞的粘附，而DP1激动剂BW245C则增加了粘附。在人食管上皮细胞上清液的趋化性测定中，只有ONO-AE1-329抑制了嗜酸性粒细胞的迁移，而butaprost或BW245C却没有。通过免疫组织化学在EoE患者的食管活检切片中检测到EP和DP受体在上皮细胞和嗜酸性粒细胞中的表达。对EoE患者进行活检的qPCR显示，在PGE2和PGD2受体中，EP4和DP1的基因表达最高。培养的食管上皮细胞对EP2和EP4均具有高基因表达。EP2和EP4受体的激活在阻抗测定法中降低了食管上皮细胞的屏障完整性。结论EP2和EP4受体的激活可能抑制嗜酸性粒细胞募集到食管粘膜。然而，它们的激活可能对食道屏障完整性产生负面影响，表明嗜酸性粒细胞而不是上皮的EP2和EP4在EoE中具有保护作用。