Background: It has been suggested that glucocorticoids might act in target tissues to increase their own intracellular availability in response to inflammatory stimuli. These mechanisms depend on the local metabolism of glucocorticoids catalyzed by 11b-hydroxysteroid dehydrogenase 1 (11b-HSD1) and 11b-hydroxysteroid dehydrogenase 2 (11b-HSD2).
Objective: This study is to investigate the effect of chronic rhinosinusitis (CRS) on expression of 11b-HSD1, 11b-HSD2, steroidogenic enzymes (cytochrome P450, family 11, subfamily B, polypeptide 1 [CYP11B1] and cytochrome P450, family 11, subfamily A, polypeptide 1 [CYP11A1]), and endogenous cortisol levels in human sinus mucosa. Expression levels were compared with those of healthy control subjects.
Methods: The expression levels of 11b-HSD1, 11b-HSD2, CYP11B1, CYP11A1, and cortisol were measured in healthy control subjects, patients with CRS with nasal polyps, and patients with CRS without nasal polyps by using real-time PCR, Western blotting, immunohistochemistry, and ELISA. Expression levels of 11b-HSD1, 11b-HSD2, CYP11B1, CYP11A1, and cortisol were determined in cultured epithelial cells treated with CRS-relevant cytokines. The conversion ratio of cortisone to cortisol was evaluated by using the small interfering RNA technique, 11b-HSD1 inhibitor, and measurement of 11b-HSD1 activity.
Results: 11b-HSD1, CYP11B1, and cortisol levels increased in patients with CRS with nasal polyps and those with CRS without nasal polyps, but 11b-HSD2 expression decreased. In cultured epithelial cells treated with IL-4, IL-5, IL-13, IL-1β, TNF-α, and TGF-b1, 11b-HSD1 expression and activity increased in parallel with expression levels of CYP11B1 and cortisol, but the production of 11b-HSD2 decreased. The small interfering RNA technique or the measurement of 11b-HSD1 activity showed that the sinus epithelium activates cortisone to cortisol in an 11b-HSDdependent manner.
Conclusion: These results indicate that CRS-relevant cytokines can modulate the expression of 11b-HSD1, 11b-HSD2, and CYP11B1 in the sinus mucosa, resulting in increasing intracellular concentrations of bioactive glucocorticoids.
- 11β-Hydroxysteroid dehydrogenase 1
- 11β-hydroxysteroid dehydrogenase 2
- CYP11A1 chronic rhinosinusitis with nasal polyps
- chronic rhinosinusitis without nasal polyps
- glucocorticoid cortisol
ASJC Scopus subject areas
- Immunology and Allergy