Differential expression of 11ß-hydroxysteroid dehydrogenase type 1 and 2 in mild and moderate/severe persistent allergic nasal mucosa and regulation of their expression by Th2 cytokines: asthma and rhinitis.
Clin Exp Allergy
; 44(2): 197-211, 2014 Feb.
Article
en En
| MEDLINE
| ID: mdl-24447082
ABSTRACT
BACKGROUND:
Glucocorticoids are used to treat allergic rhinitis, but the mechanisms by which they induce disease remission are unclear. 11ß-hydroxysteroid dehydrogenase (11ß-HSD) is a tissue-specific regulator of glucocorticoid responses, inducing the interconversion of inactive and active glucocorticoids.OBJECTIVE:
We analysed the expression and distribution patterns of 11ß-HSD1, 11ß-HSD2, and steroidogenic enzymes in normal and allergic nasal mucosa, and cytokine-driven regulation of their expression. The production levels of cortisol in normal, allergic nasal mucosa and in cultured epithelial cells stimulated with cytokines were also determined.METHODS:
The expression levels of 11ß-HSD1, 11ß-HSD2, steroidogenic enzymes (CYP11B1, CYP11A1), and cortisol in normal, mild, and moderate/severe persistent allergic nasal mucosa were assessed by real-time PCR, Western blot, immunohistochemistry, and ELISA. The expression levels of 11ß-HSD1, 11ß-HSD2, CYP11B1, CYP11A1, and cortisol were also determined in cultured nasal epithelial cell treated with IL-4, IL-5, IL-13, IL-17A, and IFN-γ. Conversion ratio of cortisone to cortisol was evaluated using siRNA technique, 11ß-HSD1 inhibitor, and the measurement of 11ß-HSD1 activity.RESULTS:
The expression levels of 11ß-HSD1, CYP11B1, and cortisol were up-regulated in mild and moderate/severe persistent allergic nasal mucosa. By contrast, 11ß-HSD2 expression was decreased in allergic nasal mucosa. In cultured epithelial cells treated with IL-4, IL-5, IL-13, and IL-17A, 11ß-HSD1 expression and activity increased in parallel with the expression levels of CYP11B1 and cortisol, but the production of 11ß-HSD2 decreased. CYP11A1 expression level was not changed in allergic nasal mucosa or in response to stimulation with cytokines. SiRNA technique or the measurement of 11ß-HSD1 activity showed that nasal epithelium activates cortisone to cortisol in a 11ß-HSD-dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE These results indicate that the localized anti-inflammatory effects of glucocorticoids are regulated by inflammatory cytokines, which can modulate the expression of 11ß-HSD1, 11ß-HSD2, and CYP11B1, and by the intracellular concentrations of bioactive glucocorticoids.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Rinitis Alérgica Perenne
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Citocinas
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Células Th2
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11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1
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11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2
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Mucosa Nasal
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Exp Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2014
Tipo del documento:
Article