Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis |
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| Institution: | 1. Department of Medicine, University of California, San Diego, La Jolla, CA, USA;2. Department of Pediatrics, University of California San Diego, San Diego, CA, USA;3. Faculty of Agriculture, The University of Tokyo, Tokyo, Japan;1. Wuhan University Health Sciences Center, Wuhan 430071, Hubei, China;2. Department Of Gynecology and Obstetrics, People''s Hospital of Jiangxi Province, Nanchang 330006, Jiangxi, China;3. Graduate School of Nanchang University, Nanchang 330006, Jiangxi, China;1. Programa de Pós-Graduação em Farmácia, Faculdade de Farmácia, Universidade Federal da Bahia, Brazil;2. Hospital Ana Nery, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Brazil;3. Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, Brazil;1. Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey;2. Şişli Etfal Education and Research Hospital, II. Internal Medicine Clinic, Department of Endocrinology, Şişli, 34387 Istanbul, Turkey;1. Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, Life Science College, Nanjing Normal University, Nanjing 210046, PR China;2. Basic Medical College, Nanjing University of Chinese Medicine, Nanjing 210046, PR China;3. College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210046, PR China;4. Hongshan Forest Zoo, Nanjing 210028, PR China |
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| 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 6 weeks 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. |
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