Mechanisms of asthma and allergic inflammationIL-13 involvement in eosinophilic esophagitis: Transcriptome analysis and reversibility with glucocorticoids
Section snippets
Cell culture
A human esophageal adenocarcinoma cell line and squamous epithelial cells (TE1, TE6, TE7, and TE13) were provided by Dr Hainault (IARC, Lyon, France). These cell lines, originally selected from esophageal tumors and well characterized by Nishihira et al,20, 21 were maintained in RPMI medium (Invitrogen, Carlsbad, Calif) supplemented with 10% FCS and 1% penicillin/streptomycin/amphotericin (Invitrogen). For primary epithelial cell culture, the culture conditions and cytokine treatments are
IL-13 expression in patients with EE
To establish the participation of IL-13 (and/or IL-4) in EE pathogenesis, we wanted first to establish whether IL-13 was overproduced in the esophageal tissue of patients with EE. By using real-time PCR analysis, there was a 16-fold increase in IL-13 mRNA in patients with EE compared with that seen in healthy patients (defined as individuals with no gastrointestinal pathology) (Fig 1, A). Interestingly, the IL-4 mRNA level was not significantly increased in our patients with EE compared with
Discussion
In this study we demonstrated that a large number of EE-associated genes are directly induced by IL-13 in esophageal keratinocytes, and we therefore implicate IL-13 as a major regulator of the keratinocyte pathways involved in EE. In EE, the esophageal tissue undergoes changes marked by an abnormal accumulation of eosinophils, mast cells,7, 13, 27 and lymphocytes7, 13; epithelial cell hyperplasia; elongation of the papillae (endothelial cells and fibroblasts); and intensive lamina propria
References (41)
- et al.
Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment
Gastroenterology
(2007) - et al.
Eosinophilic esophagitis: pathogenesis, genetics, and therapy
J Allergy Clin Immunol
(2006) - et al.
Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response
J Allergy Clin Immunol
(2001) - et al.
Cytokine regulation of IL-13Ralpha2 and IL-13Ralpha1 in vivo and in vitro
J Allergy Clin Immunol
(2003) - et al.
Eotaxin-3/CCL26 gene expression in intestinal epithelial cells is up-regulated by interleukin-4 and interleukin-13 via the signal transducer and activator of transcription 6
Int J Biochem Cell Biol
(2005) - et al.
SOCS-1 and SOCS-3 inhibit IL-4 and IL-13 induced activation of Eotaxin-3/CCL26 gene expression in HEK293 cells
Mol Immunol
(2005) - et al.
A Randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis
Gastroenterology
(2006) - et al.
Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis
Clin Gastroenterol Hepatol
(2006) - et al.
Eosinophilic esophagitis in adults: distinguishing features from gastroesophageal reflux disease: a study of 41 patients
Mod Pathol
(2006) - et al.
Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis
Clin Gastroenterol Hepatol
(2004)
Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate
Gastroenterology
Pediatric patients with eosinophilic esophagitis: an 8-year follow-up
J Allergy Clin Immunol
Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report
J Allergy Clin Immunol
Eosinophilic esophagitis
N Engl J Med
Eosinophilic gastrointestinal disorders (EGID)
J Allergy Clin Immunol
IL-13 receptors and signaling pathways: an evolving web
J Allergy Clin Immunol
Eosinophils express functional IL-13 in eosinophilic inflammatory diseases
J Immunol
Role of 5-lipoxygenase in IL-13-induced pulmonary inflammation and remodeling
J Immunol
Opposing actions of Stat1 and Stat6 on IL-13-induced up-regulation of early growth response-1 and platelet-derived growth factor ligands in pulmonary fibroblasts
J Immunol
Interleukin-13 induces dramatically different transcriptional programs in three human airway cell types
Am J Respir Cell Mol Biol
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Supported in part by National Institutes of Health grants AI070235 and AI45898 (M.E.R.), the Food Allergy and Anaphylaxis Network (M.E.R.), the Campaign Urging Research for Eosinophil Disorders, the Buckeye Foundation (M.E.R.), the Food Allergy Project (M.E.R.), the American Heart Association 0625296B (C.B.), the Thrasher Research Funds NR-0014 (C.B.), the Instituto Carlos III Fondo de Investigación Sanitaria CD05/00060 (M.V.), Public Health Service grant CA102357 (S.I.W.), the Translational Research Initiative, Cincinnati Children's Hospital Medical Center, and the DHC (NIDDK 064403).
Disclosure of potential conflict of interest: M. E. Rothenberg has consulting arrangements with Ception Therapeutics and Merck, owns stock in Ception Therapeutics, and is on the speakers' bureau for Merck. The rest of the authors have declared that they have no conflict of interest.
Transcript profiling is available online at http://cypher.cchmc.org:1104. The reader should login as a guest and select “HG-U133 genome”; experiments and gene lists are located in the folder named MRothenberg/blanchard et al.