title: Expression of 11β-hydroxysteroid dehydrogenase 1 and 2 in patients with chronic rhinosinusitis and their possible contribution to local glucocorticoid activation in sinus mucosa.
abstract: 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 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2).
  
  
  OBJECTIVE
  This study is to investigate the effect of chronic rhinosinusitis (CRS) on expression of 11β-HSD1, 11β-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 11β-HSD1, 11β-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 11β-HSD1, 11β-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, 11β-HSD1 inhibitor, and measurement of 11β-HSD1 activity.
  
  
  RESULTS
  11β-HSD1, CYP11B1, and cortisol levels increased in patients with CRS with nasal polyps and those with CRS without nasal polyps, but 11β-HSD2 expression decreased. In cultured epithelial cells treated with IL-4, IL-5, IL-13, IL-1β, TNF-α, and TGF-β1, 11β-HSD1 expression and activity increased in parallel with expression levels of CYP11B1 and cortisol, but the production of 11β-HSD2 decreased. The small interfering RNA technique or the measurement of 11β-HSD1 activity showed that the sinus epithelium activates cortisone to cortisol in an 11β-HSD-dependent manner.
  
  
  CONCLUSIONS
  These results indicate that CRS-relevant cytokines can modulate the expression of 11β-HSD1, 11β-HSD2, and CYP11B1 in the sinus mucosa, resulting in increasing intracellular concentrations of bioactive glucocorticoids.
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Soonchunhayng University, Kumi Hospital, Kyungsangbuk-Do, Kumi, Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Jun
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Hallym University, Chuncheon, Korea.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Ki Jeong
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, College of Medicine, Korea University, Seoul, Korea. Electronic address: sanghag@kumc.or.kr.
authors.forename: Sang Hag
authors.initials: SH
authors.lastname: Lee
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000235:genetics / Q000378:metabolism; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps / Q000276:immunology*; D034741:RNA, Small Interfering / Q000235:genetics; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D034741:RNA, Small Interfering; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006854:Hydrocortisone
keywords: 11β-Hydroxysteroid dehydrogenase 1; 11β-hydroxysteroid dehydrogenase 2; CYP11A1; CYP11B1; chronic rhinosinusitis without nasal polyps; chronic rhinosinusitis with nasal polyps; cortisol; glucocorticoid