Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in patients with chronic rhinosinusitis and their possible contribution to local glucocorticoid.

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Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in patients with chronic rhinosinusitis and their possible contribution to local glucocorticoid activation in sinus mucosa Young Joon Jun, MD, Se Jin Park, MD, Tae Hoon Kim, MD, Seung Hoon Lee, MD, Ki Jeong Lee, MD, Soo Min Hwang, MD, Sang Hag Lee, MD, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 4, Pages 926-934.e6 (October 2014) DOI: 10.1016/j.jaci.2014.03.033 Copyright © 2014 Terms and Conditions

Fig 1 Real-time PCR (A) and Western blot analysis (B) of 11β-HSD1, 11β-HSD2, CYP11B1, and CYP11A1 expression in normal sinus mucosa of control subjects (C; n = 25) and inflammatory sinus mucosa of patients with CRSwNP (n = 25) and patients with CRSsNP (n = 25). Western blots show representative data. *Significant difference in expression levels of 11β-HSD1, 11β-HSD2, and CYP11B1 between normal and inflammatory sinus mucosa (P < .05). Results are expressed as means ± SDs. Journal of Allergy and Clinical Immunology 2014 134, 926-934.e6DOI: (10.1016/j.jaci.2014.03.033) Copyright © 2014 Terms and Conditions

Fig 2 Real-time PCR (A, C, E, and G) and Western blot analysis (B, D, F, and H) of 11β-HSD1 (Fig 2, A and B), 11β-HSD2 (Fig 2, C and D), CYP11B1 (Fig 2, E and F), and CYP11A1 (Fig 2, G and H) expression levels in cultured epithelial cells after stimulation with IL-4, IL-5, IL-13, IFN-γ, IL-1β, TNF-α, and TGF-β1 (10 and 30 ng/mL), respectively, for 12 hours (solid bars, n = 6) or 24 hours (open bars, n = 6). Results are expressed as means ± SDs. *Statistically significant difference in 11β-HSD1, 11β-HSD2, and CYP11B1 expression levels between cytokine-stimulated cells and nonstimulated control cells (Fig 2, C). Journal of Allergy and Clinical Immunology 2014 134, 926-934.e6DOI: (10.1016/j.jaci.2014.03.033) Copyright © 2014 Terms and Conditions

Fig 3 Immunohistochemical localization of 11β-HSD1 (A-C), 11β-HSD2 (D-F), CYP11B1 (G-I), and CYP11A1 (J-L) in normal sinus mucosa (Fig 3, A, D, G, and J) and inflammatory sinus mucosa of patients with CRSwNP (Fig 3, B, E, H, and K) and patients with CRSsNP (Fig 3, C, F, I, and L). 11β-HSD1, 11β-HSD2, CYP11B1, and CYP11A1 are detected in the surface epithelium (arrowheads), submucosal glands (thick arrows), and vascular endothelium (thin arrows). Original magnification ×200. Journal of Allergy and Clinical Immunology 2014 134, 926-934.e6DOI: (10.1016/j.jaci.2014.03.033) Copyright © 2014 Terms and Conditions

Fig 4 A-C, Analysis of cortisol levels in sinus mucosa (Fig 4, A), nasal lavage fluid (Fig 4, B), and serum (Fig 4, C) of healthy subjects (n = 25), patients with CRSwNP (n = 25), and patients with CRSsNP (n = 25). D, Cortisol levels after incubation for 24 hours with ACTH (1 and 10 nmol/L). E, Cortisol levels after treatment with cortisone, 11β-HSD1 inhibitor, or both. F, Cortisol levels in siRNA transfection experiments. Results are shown as a mean of 6 independent experiments. *P < .05. Journal of Allergy and Clinical Immunology 2014 134, 926-934.e6DOI: (10.1016/j.jaci.2014.03.033) Copyright © 2014 Terms and Conditions

Fig E1 Concentration-dependent effects of cortisone on production of cortisol after treatment with 11β-HSD1 inhibitor, 11β-HSD1 siRNA, or 11β-HSD2 siRNA. *Significant difference between groups stimulated with 11β-HSD1 inhibitor versus unstimulated control subjects. **Significant difference between 11β-HSD1 or 11β-HSD2 siRNA versus control siRNA. Journal of Allergy and Clinical Immunology 2014 134, 926-934.e6DOI: (10.1016/j.jaci.2014.03.033) Copyright © 2014 Terms and Conditions

Fig E2 11β-HSD1 (A) and 11β-HSD2 (B) activity measured after stimulation with IL-4, IL-5, IL-13, IFN-γ, IL-1β, TNF-α, and TGF-β1 at a concentration of 10 ng/mL, respectively, in the presence of cortisone (100 nmol/L). *Statistically significant difference: P < .05. Journal of Allergy and Clinical Immunology 2014 134, 926-934.e6DOI: (10.1016/j.jaci.2014.03.033) Copyright © 2014 Terms and Conditions

Fig E3 Real-time PCR (A and B) and Western blot analysis (C and D) of 11β-HSD1 (Fig E3, A and C) and 11β-HSD2 (Fig E3, B and D) expression levels in cultured epithelial cells after stimulation with dexamethasone (Dex) for 24 hours. *Statistically significant difference: P < .05. Journal of Allergy and Clinical Immunology 2014 134, 926-934.e6DOI: (10.1016/j.jaci.2014.03.033) Copyright © 2014 Terms and Conditions