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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.
Jun, Y J; Park, S J; Hwang, J W; Kim, T H; Jung, K J; Jung, J Y; Hwang, G H; Lee, S H; Lee, S H.
Afiliación
  • Jun YJ; Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Rinitis Alérgica Perenne / Citocinas / Células Th2 / 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1 / 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2 / Mucosa Nasal Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Exp Allergy Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2014 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Rinitis Alérgica Perenne / Citocinas / Células Th2 / 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1 / 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2 / Mucosa Nasal Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Exp Allergy Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2014 Tipo del documento: Article