oxazolone and Eosinophilic-Esophagitis

Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition of the oesophagus with limited treatment options. No previous transgenic model has specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia.. We developed a mouse model that closely resembles EoE by utilising oxazolone haptenation in mice with transgenic overexpression of an eosinophil poietic and survival factor (interleukin (IL)-5) in resident squamous oesophageal epithelia.. Overexpression of IL-5 in the healthy oesophagus was achieved in transgenic mice (L2-IL5) using the squamous epithelial promoter Epstein-Barr virus ED-L2. Oxazolone-challenged L2-IL5 mice developed dose-dependent pan-oesophageal eosinophilia, including eosinophil microabscess formation and degranulation as well as basal cell hyperplasia. Moreover, oesophagi expressed increased IL-13 and the eosinophil agonist chemokine eotaxin-1. Treatment of these mice with corticosteroids significantly reduced eosinophilia and epithelial inflammation.. L2-IL5 mice provide a novel experimental model that can potentially be used in preclinical testing of EoE-related therapeutics and mechanistic studies identifying pathogenetic features associated with mucosal eosinophilia.

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Dexamethasone; Disease Models, Animal; Eosinophilic Esophagitis; Epithelium; Herpesvirus 4, Human; Interleukin-5; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oxazolone; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation; Viral Regulatory and Accessory Proteins