Low E-prostanoid 2 receptor levels and deficient induction of the IL-1ß/IL-1 type I receptor/COX-2 pathway: Vicious circle in patients with aspirin-exacerbated respiratory disease.
J Allergy Clin Immunol
; 137(1): 99-107.e7, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-26560040
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Oxidorreductasas Intramoleculares
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Ciclooxigenasa 2
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Interleucina-1beta
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Receptores Tipo I de Interleucina-1
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Asma Inducida por Aspirina
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Subtipo EP2 de Receptores de Prostaglandina E
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2016
Tipo del documento:
Article