title: The expression of 11β-hydroxysteroid dehydrogenase type 1 and 2 in nasal polyp-derived epithelial cells and its possible contribution to glucocorticoid activation in nasal polyp.
abstract: BACKGROUND
  The actions of glucocorticoids in target tissues depend on the local metabolism of glucocorticoids catalyzed by 11β hydroxysteroid dehydrogenase (HSD) 1 and 2. Glucocorticoids are the most effective anti-inflammatory drugs in the treatment of nasal polyps. However, the mechanisms that underlie the anti-inflammatory effects are unclear.
  
  
  OBJECTIVE
  The present study analyzed the expression of 11β-HSD1, 11β-HSD2, and steroidogenic enzymes (cytochrome P450, family 11, subfamily B, polypeptide 1 [CYP11B1]; cytochrome P450, family 11, subfamily A, polypeptide 1 [CYP11A1]) in nasal polyp tissues, and endogenous cortisol levels in nasal polyp-derived epithelial cells.
  
  
  METHODS
  The expression levels and distribution pattern of 11β-HSD1, 11β-HSD2, CYP11B1, and CYP11A1 were determined in nasal polyp tissues or nasal polyp-derived epithelial cells by using real-time polymerase chain reaction, Western blot, and immunohistochemistry testing. The expression levels of cortisol by using enzyme-linked immunosorbent assay were determined in cultured polyp-derived epithelial cells treated with adrenocorticotrophic hormone (ACTH), 11β-HSD1 inhibitor, or small interfering ribonucleic acid technique. The effect of glucocorticoids on the expression levels of these enzymes was investigated in cultured cells.
  
  
  RESULTS
  Expressed in nasal polyp tissues and nasal polyp-derived epithelial cells were 11β-HSD1, 11β-HSD2, CYP11B1, and CYP11A1. Cortisol production in cultured epithelial cells was decreased in cells treated with 11β-HSD1 small interfering ribonucleic acid or inhibitor, compared with nontreated cells. Cultured cells treated with adrenocorticotropic hormone induced increased cortisol production. 11β-HSD1 expression levels were upregulated in cells treated with glucocorticoid.
  
  
  CONCLUSIONS
  Analysis of these results indicated that 11β-HSD1 expressed in polyp-derived epithelial cells may be involved in the anti-inflammatory function of glucocorticoid in the treatment of nasal polyps, which contributes to increased levels of endogenous cortisol.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Korea University, Seoul, South Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Kook
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kyung Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Sae Hee
authors.initials: SH
authors.lastname: Lim
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kang
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*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D066298:In Vitro Techniques; D009298:Nasal Polyps / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006854:Hydrocortisone