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Differential expression of 11β‐hydroxysteroid dehydrogenase type 1 and 2 in mild and moderate/severe persistent allergic nasal mucosa and regulation of their expression by Th2 cytokines
Author(s) -
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.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12195
Subject(s) - mucous membrane of nose , endocrinology , medicine , glucocorticoid , cortisone , cytokine , 11β hydroxysteroid dehydrogenase type 1 , immunology , western blot , biology , dehydrogenase , enzyme , gene , biochemistry
Summary Background Glucocorticoids are used to treat allergic rhinitis, but the mechanisms by which they induce disease remission are unclear. 11β‐hydroxysteroid dehydrogenase (11β‐ 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 11β‐ HSD 1, 11β‐ HSD 2, 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 11β‐ HSD 1, 11β‐ HSD 2, steroidogenic enzymes ( CYP 11B1, CYP 11A1), 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 11β‐ HSD 1, 11β‐ HSD 2, CYP 11B1, CYP 11A1, 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 si RNA technique, 11β‐ HSD 1 inhibitor, and the measurement of 11β‐ HSD 1 activity. Results The expression levels of 11β‐ HSD 1, CYP 11B1, and cortisol were up‐regulated in mild and moderate/severe persistent allergic nasal mucosa. By contrast, 11β‐ HSD 2 expression was decreased in allergic nasal mucosa. In cultured epithelial cells treated with IL ‐4, IL ‐5, IL ‐13, and IL ‐17A, 11β‐ HSD 1 expression and activity increased in parallel with the expression levels of CYP 11B1 and cortisol, but the production of 11β‐ HSD 2 decreased. CYP 11A1 expression level was not changed in allergic nasal mucosa or in response to stimulation with cytokines. Si RNA technique or the measurement of 11β‐ HSD 1 activity showed that nasal epithelium activates cortisone to cortisol in a 11β‐ 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 11β‐ HSD 1, 11β‐ HSD 2, and CYP 11B1, and by the intracellular concentrations of bioactive glucocorticoids.