alexa Remodeling and fibrosis in chronic eosinophil inflammation.


Journal of Hepatology and Gastrointestinal disorders

Author(s): Aceves SS

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Abstract Chronic eosinophilic inflammation has been associated with tissue remodeling in a number of disease states including the hypereosinophilic syndrome (HES), asthma, and, more recently, eosinophilic esophagitis (EoE). Remodeling occurs in the epithelial and subepithelial esophageal tissue, and includes basal zone hyperplasia, epithelial mesenchymal transition, fibrosis, angiogenesis, and smooth muscle hypertrophy/hyperplasia. Previously, research on the clinical impacts of tissue remodeling has been limited by a paucity of human tissue. However, in EoE, recurrent biopsies are required for diagnosis and management. As such, investigators are able to study the associations between tissue changes and clinical disease features. A number of profibrotic and proangiogenic factors are elevated in EoE, including TGF-β1, CCL-18, FGF-9, VEGF, and VCAM-1. Both eosinophils and mast cells produce a number of these factors. TGF-β1 appears to be a master regulator of end-organ dysfunction in EoE and can cause esophageal epithelial mesenchymal transition, fibrosis, and smooth muscle contraction. The requirement for eosinophils, the eosinophilopoietic interleukin, IL-5, and the canonical TGF-β1 signaling pathway for EoE-associated fibrosis, has been invoked using gene-deficient mice. The clinical consequences of eosinophil-associated tissue fibrosis can be devastating, such as endomyocardial fibrosis and heart failure in HES. In EoE, tissue remodeling appears to be the mechanism for multiple cardinal disease complications including esophageal rigidity, strictures, narrowing, and food impactions, as well as the clinical hallmark of dysphagia. Therapies that may be able to reduce or reverse EoE-associated remodeling include topical corticosteroids, anti-IL-5, and food antigen avoidance. 2014 S. Karger AG, Basel.
This article was published in Dig Dis and referenced in Journal of Hepatology and Gastrointestinal disorders

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