Prostaglandin and cannabinoid receptors in EoE

Eosinophilic esophagitis (EoE) is a chronic, antigen- and immune cell-mediated inflammation of the esophagus. The disease is characterized by intense infiltration of eosinophils into the esophageal mucosa. Eosinophils belong to the group of white blood cells with cytotoxic enzymes. Dysphagia is one of the early symptoms of EoE. It has been long regarded as a rare disease but through advanced diagnostic methods and actual higher number of cases, the incidence of EoE has increased in the past years. Although thought to be induced primarily by an aberrant immune response the exact cause of EoE remains unclear. A compound inhibiting the prostaglandin (PG) D2 receptor has been recently shown to improve disease symptoms of EoE suggesting a regulatory role for bioactive lipids like prostaglandins and endocannabinoids in the development of disease. These mediators are key players in inflammation. Similar to prostaglandins, endocannabinoids regulate tissue homeostasis. The project, therefore, explores the role of PGD2, PGE2 and endocannabinoids, and of their receptors in white blood cells of subjects with and without EoE. Esophageal mucosal biopsies from patients with EoE and gastro-esophageal reflux, and from subjects with no esophageal disease are collected and used to study expression of PGD2, PGE2 and cannabinoid receptors. In biopsies, the content of PGD2, PGE2 and endocannabinoids are measured by mass spectrometry. In cell culture experiments, we will explore whether eosinophils interact with mucosal epithelial cells of the esophagus. Prostaglandin-producing enzymes and receptors of the endocannabinoid system are highly amenable to pharmacological treatment. Since the role of the two systems in EoE are hardly known, the proposal explores new ground. The prostaglandin and the endocannabinoid system could reveal much needed biomarkers of disease while investigating the two systems could open up new therapeutical possibilities of EoE treatment.