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Growth factors and eosinophilic esophagitis

Carine Blanchard
PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) is an esophageal disease characterized by an accumulation of eosinophils in the esophagus, which is normally devoid of eosinophils. The interest of the scientific community in EoE has grown considerably over the past two decades, and understanding of the molecular mechanisms involved in this disease has increased greatly in the last 2 years. RECENT FINDINGS: Important new insights into the pathogenesis of EoE recently have been achieved...
July 2015: Current Opinion in Gastroenterology
Evan S Dellon, Spencer Rusin, Jessica H Gebhart, Shannon Covey, Leana L Higgins, RoseMary Beitia, Olga Speck, Kimberly Woodward, John T Woosley, Nicholas J Shaheen
OBJECTIVES: Noninvasive biomarkers would be valuable for diagnosis and monitoring of eosinophilic esophagitis (EoE). The aim of this study was to determine the utility of a panel of serum biomarkers for the diagnosis and management of EoE. METHODS: We conducted a prospective cohort study of consecutive adults undergoing outpatient esophagogastroduodenoscopy. Incident cases of EoE were diagnosed per consensus guidelines; controls had gastroesophageal reflux disease (GERD) or dysphagia and did not meet the EoE criteria...
June 2015: American Journal of Gastroenterology
Marc E Rothenberg
Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute to risk for EoE, particularly early-life events. Disease pathogenesis involves activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]), impaired barrier function (mediated by loss of desmoglein-1), increased production and/or activity of transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells...
May 2015: Gastroenterology
Neha Malhotra, Jeremiah Levine
Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal inflammatory disease associated with esophageal dysfunction resulting from severe inflammation. The incidence and prevalence of EoE have been increasing in the past decade; however, the reason for this increase is unclear. There is a chronic inflammatory infiltrate that is present in EoE which promotes inflammation, symptoms, and dysfunction. In addition to eosinophils, interleukin (IL)-5 expressing T cells, B cells, eotaxin-3, IL-13, and IgE-bearing mast cells are present in EoE and are thought to contribute to the disease process...
December 2014: Current Problems in Pediatric and Adolescent Health Care
M Rochman, A V Kartashov, J M Caldwell, M H Collins, E M Stucke, K Kc, J D Sherrill, J Herren, A Barski, M E Rothenberg
Although interleukin (IL)-13 and neurotrophins are functionally important for the pathogenesis of immune responses, the interaction of these pathways has not been explored. Herein, by interrogating IL-13-induced responses in human epithelial cells we show that neurotrophic tyrosine kinase receptor, type 1 (NTRK1), a cognate, high-affinity receptor for nerve growth factor (NGF), is an early transcriptional IL-13 target. Induction of NTRK1 was accompanied by accumulation of activating epigenetic marks in the promoter; transcriptional and epigenetic changes were signal transducer and activator of transcription 6 dependent...
July 2015: Mucosal Immunology
Mayumi Raheem, Steven T Leach, Andrew S Day, Daniel A Lemberg
Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution...
2014: Frontiers in Pediatrics
Florian Rieder, Ilche Nonevski, Jie Ma, Zhufeng Ouyang, Gail West, Cheryl Protheroe, Giovanni DePetris, Anja Schirbel, James Lapinski, John Goldblum, Tracey Bonfield, Rocio Lopez, Karen Harnett, James Lee, Ikuo Hirano, Gary Falk, Piero Biancani, Claudio Fiocchi
BACKGROUND & AIMS: Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. METHODS: Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls)...
May 2014: Gastroenterology
Solange M Abdulnour-Nakhoul, Youhanna Al-Tawil, Alex A Gyftopoulos, Karen L Brown, Molly Hansen, Kathy F Butcher, Alexandra P Eidelwein, Robert A Noel, Edd Rabon, Allison Posta, Nazih L Nakhoul
Eosinophilic esophagitis (EoE), an inflammatory atopic disease of the esophagus, causes massive eosinophil infiltration, basal cell hyperplasia, and sub-epithelial fibrosis. To elucidate cellular and molecular factors involved in esophageal tissue damage and remodeling, we examined pinch biopsies from EoE and normal pediatric patients. An inflammation gene array confirmed that eotaxin-3, its receptor CCR3 and interleukins IL-13 and IL-5 were upregulated. An extracellular matrix (ECM) gene array revealed upregulation of CD44 & CD54, and of ECM proteases (ADAMTS1 & MMP14)...
August 2013: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Iris M Otani, Arjun A Anilkumar, Robert O Newbury, Monica Bhagat, Lisa Y Beppu, Ranjan Dohil, David H Broide, Seema S Aceves
BACKGROUND: Eosinophilic esophagitis (EoE) is a clinicopathologic entity of increasing worldwide prevalence. IL-5 is essential for eosinophil trafficking, and anti-IL-5 therapy decreases esophageal eosinophilia. EoE is associated with prominent mast cell infiltration. OBJECTIVE: We investigated whether anti-IL-5 (mepolizumab) treatment reduced esophageal mast cell accumulation in biopsy specimens from pediatric patients with EoE from a previous randomized anti-IL-5 trial...
June 2013: Journal of Allergy and Clinical Immunology
Jenny Weinbrand-Goichberg, Idit Segal, Adi Ovadia, Arie Levine, Ilan Dalal
Eosinophilic esophagitis (EoE) is an emerging disease defined by esophageal dysfunction, by typical endoscopic findings and by abnormal eosinophilic inflammation within the esophagus. Eosinophilic accumulation in the esophagus occurs as a result of esophageal overexpression of pro-inflammatory mediators, including T cells and mast cells, cytokines such as interleukin (IL)-13, IL-5 and IL-15, as well as chemoattractants (eotaxin and transforming growth factor-β1, fibroblast growth factor and the newly characterized gene--thymic stromal lymphopoietin, which is a key regulator of allergic sensitization initiation)...
July 2013: Immunologic Research
Robert M Kirberger, Sarah J Clift, Erna van Wilpe, Eran Dvir
Spirocerca lupi causes a caudal esophageal mass in dogs which may be accompanied by aortic changes and caudal thoracic spondylitis. Previous literature hypothesized that the spondylitis was caused by either aberrant larval migration or was secondary to the inflammation caused by the aortic migration. The current study aimed to evaluate these hypotheses. Ten dogs of various breeds and ages with radiographic evidence of spondylitis, which were necropsied, had the affected vertebrae removed and prepared for light and transmission electron microscopy examination...
July 1, 2013: Veterinary Parasitology
Amanda B Muir, Diana M Lim, Alain J Benitez, Prasanna Modayur Chandramouleeswaran, Anna J Lee, Eduardo D Ruchelli, Jonathan M Spergel, Mei-Lun Wang
BACKGROUND: Esophageal fibrosis is a complication of eosinophilic esophagitis (EoE) which has been attributed to both subepithelial fibrosis and to epithelial to mesenchymal transition (EMT), a process by which epithelial cells acquire mesenchymal features. Common to both causes of EoE-fibrosis is the notion that granulocyte-derived TGF-β, induces myofibroblast differentiation of the target cell. To date, the role of esophageal epithelial cells as effector cells in esophageal fibrosis has never been explored...
April 1, 2013: Experimental Cell Research
Edaire Cheng, Rhonda F Souza, Stuart J Spechler
Eosinophilic esophagitis (EoE) is a recently recognized, immune-mediated disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. The chronic esophageal eosinophilia of EoE is associated with tissue remodeling that includes epithelial hyperplasia, subepithelial fibrosis, and hypertrophy of esophageal smooth muscle. This remodeling causes the esophageal rings and strictures that frequently complicate EoE and underlies the mucosal fragility that predisposes to painful mucosal tears in the EoE esophagus...
December 1, 2012: American Journal of Physiology. Gastrointestinal and Liver Physiology
Amir F Kagalwalla, Noorain Akhtar, Samantha A Woodruff, Bryan A Rea, Joanne C Masterson, Vincent Mukkada, Kalyan R Parashette, Jian Du, Sophie Fillon, Cheryl A Protheroe, James J Lee, Katie Amsden, Hector Melin-Aldana, Kelley E Capocelli, Glenn T Furuta, Steven J Ackerman
BACKGROUND: Mechanisms underlying esophageal remodeling with subepithelial fibrosis in subjects with eosinophilic esophagitis (EoE) have not been delineated. OBJECTIVES: We sought to explore a role for epithelial mesenchymal transition (EMT) in subjects with EoE and determine whether EMT resolves with treatment. METHODS: Esophageal biopsy specimens from 60 children were immunostained for epithelial (cytokeratin) and mesenchymal (vimentin) EMT biomarkers, and EMT was quantified...
May 2012: Journal of Allergy and Clinical Immunology
Rabindranath Persad, Hien Q Huynh, Li Hao, Jacqueline R Ha, Consolato Sergi, Rahul Srivastava, Sujata Persad
OBJECTIVES: Eosinophilic esophagitis (EoE) is a clinicopathologic diagnosis characterized by inflammation and infiltration of eosinophils at the esophageal mucosa. The underlying etiology of EoE remains elusive. Inflammatory diseases, such as asthma, are associated with structural remodeling of the airways, which includes angiogenesis. The aims of this study were to determine the angiogenic profile of esophageal mucosa in children presenting with EoE and to evaluate the putative mechanism(s) underlying the early inflammatory angiogenic response observed in EoE...
September 2012: Journal of Pediatric Gastroenterology and Nutrition
Eitan Rubinstein, Jae Youn Cho, Peter Rosenthal, James Chao, Marina Miller, Alexa Pham, Seema S Aceves, Ajit Varki, David H Broide
OBJECTIVES: Eosinophilic esophagitis (EoE) is a disorder characterized histologically by tissue eosinophilia. Sialic acid-binding immunoglobulin-like lectin (Siglec-F) is a receptor highly expressed on mouse eosinophils and mediates eosinophilic apoptosis. We investigated whether administration of an anti-Siglec-F Ab would reduce esophageal eosinophilic inflammation and remodeling in a mouse model of egg ovalbumin (OVA)-induced EoE. SUBJECTS AND METHODS: Three groups of mice were studied (no OVA, OVA + anti-Siglec-F Ab, and OVA + isotype control Ab)...
October 2011: Journal of Pediatric Gastroenterology and Nutrition
Alfredo J Lucendo, Angel Arias, Livia C De Rezende, Jose Luis Yagüe-Compadre, Teresa Mota-Huertas, Sonia González-Castillo, Rubén A Cuesta, José M Tenias, Teresa Bellón
BACKGROUND: Recent research shows that both pediatric and adult patients with eosinophilic esophagitis (EoE) experience esophageal remodeling marked by increased collagen deposition in which TGF-β plays an important role. However, limited data are available on the intensity and reversibility of fibrous remodeling in adults with EoE. OBJECTIVE: We sought to analyze differences in collagen deposition in the lamina propria (LP) and profibrogenic cytokine gene expression along with other changes induced by prolonged treatment with fluticasone propionate in adults with EoE...
November 2011: Journal of Allergy and Clinical Immunology
E S Dellon, J J Bower, T O Keku, X Chen, C R Miller, J T Woosley, R C Orlando, N J Shaheen
The pathogenesis of eosinophilic esophagitis (EoE) is incompletely understood. In certain eosinophilic diseases, activation of tyrosine kinase after fusion of the Fip1-like-1 and platelet-derived growth factor receptor-α genes (F-P fusion gene) mediates eosinophilia via downstream effectors such as extracellular-regulated kinase (ERK1/2) and signal transducers and activators of transcription (STAT5). This mechanism has not been examined in EoE. Our aim was to detect the F-P fusion gene, pERK1/2, and pSTAT5 in esophageal tissue from patients with EoE, gastroesophageal reflux disease (GERD), and normal controls...
February 2012: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
D J Mulder, C J Justinich
Eosinophilic esophagitis (EoE) has been increasingly recognized as a unique clinicopathological entity over the past two decades. In this short time, the mechanisms of a complex disease have begun to emerge. Patient studies suggest that EoE is an immunologic disease related to atopy. At the cellular level, eosinophils, mast cells, and B and T lymphocytes are increased in the esophageal mucosa in a patchy distribution throughout the length of the esophagus. Laboratory investigations have implicated aeroallergens, food allergens, and a unique T helper type 2 cytokine profile...
March 2011: Mucosal Immunology
Seema S Aceves, Diana Chen, Robert O Newbury, Ranjan Dohil, John F Bastian, David H Broide
BACKGROUND: Increased numbers of mast cells are present in the esophageal epithelium in patients with eosinophilic esophagitis (EE). However, mast cell infiltration into the esophageal lamina propria (LP) and smooth muscle (SM) and the effects of their products on SM function has not been determined. OBJECTIVE: We investigated mast cell localization and characterization in esophageal SM, the functional significance of mast cell TGF-β1 expression to contraction of human esophageal smooth muscle (HESM) cells in vitro, and the effect of topical corticosteroids on the number of tryptase-positive (MC(T)) and chymase-positive (MC(C)) mast cells in patients with EE...
December 2010: Journal of Allergy and Clinical Immunology
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