Abstract
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-HSD1, 11β-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 11β-HSD1, 11β-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 11β-HSD1, 11β-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, 11β-HSD1 inhibitor, and the measurement of 11β-HSD1 activity. Results: The expression levels of 11β-HSD1, CYP11B1, and cortisol were up-regulated in mild and moderate/severe persistent allergic nasal mucosa. By contrast, 11β-HSD2 expression was decreased in allergic nasal mucosa. In cultured epithelial cells treated with IL-4, IL-5, IL-13, and IL-17A, 11β-HSD1 expression and activity increased in parallel with the expression levels of CYP11B1 and cortisol, but the production of 11β-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 11β-HSD1 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-HSD1, 11β-HSD2, and CYP11B1, and by the intracellular concentrations of bioactive glucocorticoids.
| Original language | English |
|---|---|
| Pages (from-to) | 197-211 |
| Number of pages | 15 |
| Journal | Clinical and Experimental Allergy |
| Volume | 44 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2014 Feb 1 |
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Keywords
- 11β-HSD1
- 11β-HSD2
- CYP11A1
- CYP11B1
- Mild persistent allergic rhinitis
- Moderate/severe persistent allergic rhinitis
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
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. / Jun, Y. J.; Park, S. J.; Hwang, J. W.; Kim, Tae-Hoon; Jung, K. J.; Jung, J. Y.; Hwang, G. H.; Lee, Sang Hag; Lee, S. H.
In: Clinical and Experimental Allergy, Vol. 44, No. 2, 01.02.2014, p. 197-211.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Jun, Y. J.
AU - Park, S. J.
AU - Hwang, J. W.
AU - Kim, Tae-Hoon
AU - Jung, K. J.
AU - Jung, J. Y.
AU - Hwang, G. H.
AU - Lee, Sang Hag
AU - Lee, S. H.
PY - 2014/2/1
Y1 - 2014/2/1
N2 - 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-HSD1, 11β-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 11β-HSD1, 11β-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 11β-HSD1, 11β-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, 11β-HSD1 inhibitor, and the measurement of 11β-HSD1 activity. Results: The expression levels of 11β-HSD1, CYP11B1, and cortisol were up-regulated in mild and moderate/severe persistent allergic nasal mucosa. By contrast, 11β-HSD2 expression was decreased in allergic nasal mucosa. In cultured epithelial cells treated with IL-4, IL-5, IL-13, and IL-17A, 11β-HSD1 expression and activity increased in parallel with the expression levels of CYP11B1 and cortisol, but the production of 11β-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 11β-HSD1 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-HSD1, 11β-HSD2, and CYP11B1, and by the intracellular concentrations of bioactive glucocorticoids.
AB - 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-HSD1, 11β-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 11β-HSD1, 11β-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 11β-HSD1, 11β-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, 11β-HSD1 inhibitor, and the measurement of 11β-HSD1 activity. Results: The expression levels of 11β-HSD1, CYP11B1, and cortisol were up-regulated in mild and moderate/severe persistent allergic nasal mucosa. By contrast, 11β-HSD2 expression was decreased in allergic nasal mucosa. In cultured epithelial cells treated with IL-4, IL-5, IL-13, and IL-17A, 11β-HSD1 expression and activity increased in parallel with the expression levels of CYP11B1 and cortisol, but the production of 11β-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 11β-HSD1 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-HSD1, 11β-HSD2, and CYP11B1, and by the intracellular concentrations of bioactive glucocorticoids.
KW - 11β-HSD1
KW - 11β-HSD2
KW - CYP11A1
KW - CYP11B1
KW - Mild persistent allergic rhinitis
KW - Moderate/severe persistent allergic rhinitis
UR - http://www.scopus.com/inward/record.url?scp=84892727709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892727709&partnerID=8YFLogxK
U2 - 10.1111/cea.12195
DO - 10.1111/cea.12195
M3 - Article
VL - 44
SP - 197
EP - 211
JO - Clinical and Experimental Allergy
JF - Clinical and Experimental Allergy
SN - 0954-7894
IS - 2
ER -