Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis.

Abstract

Studies of AMCase inhibition in mouse models of lung eosinophilic inflammation have produced conflicting results with some studies demonstrating inhibition of eosinophilic inflammation and others not. No studies have investigated the role of AMCase inhibition in eosinophilic esophagitis (EoE). We have used a mouse model of egg (OVA) induced EoE to determine whether pharmacologic inhibition of AMCase with allosamidin reduced eosinophilic inflammation and remodeling in the esophagus in EoE. Administration of intra-esophageal OVA for 6weeks to BALB/c mice induced increased levels of esophageal eosinophils, mast cells, and features of esophageal remodeling (fibrosis, basal zone hyperplasia, deposition of the extracellular matrix protein fibronectin). Administration of intraperitoneal (ip) allosamidin to BALB/c mice significantly inhibited AMCase enzymatic activity in the esophagus. Pharmacologic inhibition of AMCase with ip allosamidin inhibited both OVA induced increases in esophageal eosinophilic inflammation and OVA induced esophageal remodeling (fibrosis, epithelial basal zone hyperplasia, extracellular matrix deposition of fibronectin). This inhibition of eosinophilic inflammation in the esophagus by ip allosamidin was associated with reduced eotaxin-1 expression in the esophagus. Oral allosamidin inhibited eosinophilic inflammation in the epithelium but did not inhibit esophageal remodeling. These studies suggest that pharmacologic inhibition of AMCase results in inhibition of eosinophilic inflammation and remodeling in the esophagus in a mouse model of egg induced EoE partially through effects in the esophagus on reducing chemokines (i.e. eotaxin-1) implicated in the pathogenesis of EoE.

• Authors: Jae Youn Cho, Peter Rosenthal, Marina Miller, Alexa Pham, Seema Aceves, Shohei Sakuda, David H Broide
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 18 Issue 1 Pg. 35-42 (Jan 2014) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 24239745 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Allergens
• Chemokine CCL11
• Enzyme Inhibitors
• Inflammation Mediators
• Trisaccharides
• allosamidin
• Ovalbumin
• AMCase, mouse
• Chitinases
• Acetylglucosamine

Topics

• Acetylglucosamine (administration & dosage, analogs & derivatives)
• Allergens (immunology)
• Animals
• Cells, Cultured
• Chemokine CCL11 (genetics, metabolism)
• Chitinases (metabolism)
• Disease Models, Animal
• Eggs (adverse effects)
• Enzyme Inhibitors (administration & dosage)
• Eosinophilic Esophagitis (chemically induced, drug therapy, immunology)
• Esophagus (drug effects, immunology, pathology)
• Female
• Fibrosis
• Humans
• Hyperplasia
• Hypersensitivity, Immediate (chemically induced, drug therapy, immunology)
• Inflammation Mediators (metabolism)
• Mice, Inbred BALB C
• Molecular Targeted Therapy
• Ovalbumin (adverse effects, immunology)
• Trisaccharides (administration & dosage)