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

Durchschein, F.; Eherer, Andreas; Grill, Magdalena; Sturm, Eva; Langner, Cord; Högenauer, Christoph; Schicho, Rudolf

doi:10.1007/s10620-019-05623-5

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…In this study, we show that EP4 agonist L-902,688 therapy increased immunosuppressive activity of intrinsic PMN- and M-MDSCs in a dose-dependent manner, correlating to our in vitro results. Reduced numbers of eosinophils observed in the BALF of asthmatic mice treated with the EP4 agonist L-902,688 are consistent with previous findings, where ONO-AE1-329, another selective EP4 agonist, inhibited eosinophil function and transendothelial migration ( 39 , 40 ). In line with previous findings ( 22 ), we showed that the EP4 agonist L-902,688 ameliorates histological inflammatory features in the lung of asthmatic mice, by inhibiting inflammatory cell infiltration into both peribronchial and perivascular regions.…”

Section: Discussionsupporting

confidence: 92%

Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4

Geffen

Deißler²,

Beer‐Hammer

et al. 2021

Front. Immunol.

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Emerging evidence suggests a mechanistic role for myeloid-derived suppressor cells (MDSCs) in lung diseases like asthma. Previously, we showed that adoptive transfer of MDSCs dampens lung inflammation in murine models of asthma through cyclooxygenase-2 and arginase-1 pathways. Here, we further dissected this mechanism by studying the role and therapeutic relevance of the downstream mediator prostaglandin E2 receptor 4 (EP4) in a murine model of asthma. We adoptively transferred MDSCs generated using an EP4 agonist in a murine model of asthma and studied the consequences on airway inflammation. Furthermore, pegylated human arginase-1 was used to model MDSC effector activities. We demonstrate that the selective EP4 agonist L-902,688 increased the number and suppressive activity of MDSCs through arginase-1 and nitric oxide synthase-2. These results showed that adoptive transfer of EP4-primed MDSCs, EP4 agonism alone or arginase-1 administration ameliorated lung inflammatory responses and histopathological changes in asthmatic mice. Collectively, our results provide evidence that MDSCs dampen airway inflammation in murine asthma through a mechanism involving EP4.

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Section: Discussionsupporting

confidence: 92%

Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4

Geffen

Deißler²,

Beer‐Hammer

et al. 2021

Front. Immunol.

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“…Of those, eosinophils were reported to express EP2 and EP4 receptors [ 78 , 213 , 214 ]. Of note, Durchschein et al recently demonstrated a decreased expression of EP2 and EP4 receptors on blood eosinophils in a small cohort of patients with eosinophilic esophagitis [ 215 ].…”

Section: Eicosanoids and Eosinophilsmentioning

confidence: 99%

Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids

Knuplez

Sturm

Marsche

2021

IJMS

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Eosinophils are important effector cells involved in allergic inflammation. When stimulated, eosinophils release a variety of mediators initiating, propagating, and maintaining local inflammation. Both, the activity and concentration of secreted and cytosolic phospholipases (PLAs) are increased in allergic inflammation, promoting the cleavage of phospholipids and thus the production of reactive lipid mediators. Eosinophils express high levels of secreted phospholipase A2 compared to other leukocytes, indicating their direct involvement in the production of lipid mediators during allergic inflammation. On the other side, eosinophils have also been recognized as crucial mediators with regulatory and homeostatic roles in local immunity and repair. Thus, targeting the complex network of lipid mediators offer a unique opportunity to target the over-activation and ‘pro-inflammatory’ phenotype of eosinophils without compromising the survival and functions of tissue-resident and homeostatic eosinophils. Here we provide a comprehensive overview of the critical role of phospholipase-derived lipid mediators in modulating eosinophil activity in health and disease. We focus on lysophospholipids, polyunsaturated fatty acids, and eicosanoids with exciting new perspectives for future drug development.

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“…PGE2 attaches to epithelial cells via EP2 and/or EP4, increasing cAMP levels and triggering adenylate cyclase to relax airway smooth muscle. This process helps to regulate asthma triggered on by exercise and bronchospasm [12,13]. In the gastrointestinal system, The smooth muscles of the ileum, stomach, and small intestine contract upon EP3 receptor activation [5,14].…”

Section: Introductionmentioning

confidence: 99%

PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway

Su,

Zhou,

Chen

et al. 2024

BMC Urol

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Background This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. Methods By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. Results The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P < 0.01). Smooth muscle cells treated with PGE2 displayed increased cAMP and phosphorylated PKA. Conclusions PGE2 binding to EP2 induces ureteral relaxation through the cAMP-PKA pathway. This will provide a new theoretical basis for the development of new therapeutic approaches for the use of PGE2 in the treatment of ureteral stones.

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

Cited by 6 publications

References 43 publications

Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4

Myeloid-Derived Suppressor Cells Dampen Airway Inflammation Through Prostaglandin E2 Receptor 4

Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids

PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway

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