| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Machado-Carvalho, Liliana Martín, Margarita Torres, Rosa Gabasa, Marta Alobid, Isam Mullol, Joaquim Pujols, Laura Roca-Ferrer, Jordi Picado, Cesar |
| Description |
Author Affiliation: Machado-Carvalho L ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain); Martín M ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain); Torres R ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain); Gabasa M ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain); Alobid I ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain); Mullol J ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain); Pujols L ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain); Roca-Ferrer J ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain); Picado C ( Clinical and Experimental Respiratory Immunoallergy, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain) |
| Abstract |
BACKGROUND: We hypothesized that the 2 reported alterations in aspirin-exacerbated respiratory disease (AERD), reduced expression/production of COX-2/prostaglandin (PG) E2 and diminished expression of E-prostanoid (EP) 2 receptor, are closely linked. OBJECTIVE: We sought to determine the mechanisms involved in the altered regulation of the COX pathway in patients with AERD. METHODS: Fibroblasts were obtained from nasal mucosa; samples of control subjects (NM-C, n = 8) and from nasal polyps from patients with aspirin-exacerbated respiratory disease (NP-AERD, n = 8). Expression of the autocrine loop components regulating PGE2 production and signaling, namely IL-1 type I receptor (IL-1RI), COX-2, microsomal prostaglandin E synthase 1 (mPGES-1), and EP receptors, was assessed at baseline and after stimulation with IL-1ß, PGE2, and specific EP receptor agonists. RESULTS: Compared with NM-C fibroblasts, basal expression levels of IL-1RI and EP2 receptor were lower in NP-AERD fibroblasts. IL-1ß-induced IL-1RI, COX-2, and mPGES-1 expression levels were also lower in these cells. Levels of IL-1RI positively correlated with COX-2 and mPGES-1 expression in both NM-C and NP-AERD fibroblasts. Incubation with either exogenous PGE2 or selective EP2 agonist significantly increased expression of IL-1RI in NM-C fibroblasts and had hardly any effect on NP-AERD fibroblasts. Alterations in IL-1RI, COX-2, and mPGES-1 expression that were found in NP-AERD fibroblasts were corrected when EP2 receptor expression was normalized by transfection of NP-AERD fibroblasts. CONCLUSION: Altered expression of EP2 in patients with AERD contributes to deficient induction of IL-1RI, reducing the capacity of IL-1ß to increase COX-2 and mPGES-1 expression, which results in low PGE2 production. This impairment in the generation of PGE2 subsequently reduces its ability to induce IL-1RI. |
| File Format |
HTM / HTML |
| ISSN |
00916749 |
| e-ISSN |
10976825 |
| Journal |
Journal of Allergy and Clinical Immunology |
| Issue Number |
1 |
| Volume Number |
137 |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2016-01-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Discipline Immunology Asthma, Aspirin-induced Metabolism Cyclooxygenase 2 Interleukin-1beta Intramolecular Oxidoreductases Receptors, Interleukin-1 Type I Receptors, Prostaglandin E, Ep2 Subtype Alprostadil Analogs & Derivatives Pharmacology Aspirin Cells, Cultured Genetics Dinoprostone Fibroblasts Drug Effects Nasal Mucosa Cytology Nasal Polyps Rna, Messenger Agonists Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
