Interleukin-4 in the Generation of the AERD Phenotype: Implications for Molecular Mechanisms Driving Therapeutic Benefit of Aspirin Desensitization
| العنوان: | Interleukin-4 in the Generation of the AERD Phenotype: Implications for Molecular Mechanisms Driving Therapeutic Benefit of Aspirin Desensitization |
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| المؤلفون: | Larry Borish, Spencer C. Payne, John W. Steinke |
| المصدر: | Journal of Allergy |
| بيانات النشر: | Hindawi Publishing Corporation, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | biology, Leukotriene C4, business.industry, Review Article, Pharmacology, Mast cell, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Downregulation and upregulation, Eosinophil activation, Immunology, biology.protein, Immunology and Allergy, Medicine, Cyclooxygenase, Prostaglandin E2, business, Receptor, Interleukin 4, medicine.drug |
| الوصف: | Aspirin-exacerbated respiratory disease (AERD) is explained in part by over-expression of 5-lipoxygenase, leukotriene C4 synthase (LTC4S) and the cysteinyl leukotriene (CysLT) receptors (CysLT1 and 2), resulting in constitutive over-production of CysLTs and the hyperresponsiveness to CysLTs that occurs with aspirin ingestion. Increased levels of IL-4 have been found in the sinus mucosa and nasal polyps of AERD subjects. Previous studies demonstrated that IL-4 is primarily responsible for the upregulation of LTC4S by mast cells and the upregulation of CysLT1 and 2 receptors on many immune cell types. Prostaglandin E2 (PGE2) acts to prevent CysLT secretion by inhibiting mast cell and eosinophil activation. PGE2 concentrations are reduced in AERD reflecting diminished expression of cyclooxygenase (COX)-2. IL-4 can inhibit basal and stimulated expression of COX-2 and microsomal PGE synthase 1 leading to decreased capacity for PGE2 secretion. Thus, IL-4 plays an important pathogenic role in generating the phenotype of AERD. This review will examine the evidence supporting this hypothesis and describe a model of how aspirin desensitization provides therapeutic benefit for AERD patients. |
| اللغة: | English |
| تدمد: | 1687-9791 1687-9783 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::16aa0bf5f3ec6d293f0d285e005bce29Test http://europepmc.org/articles/PMC3259477Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....16aa0bf5f3ec6d293f0d285e005bce29 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16879791 16879783 |
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