title: Increase of 27-hydroxycholesterol in the airways of patients with COPD: possible role of 27-hydroxycholesterol in tissue fibrosis.
abstract: BACKGROUND
  27-Hydroxycholesterol (27-OHC) is produced from cholesterol by sterol 27-hydroxylase as an intermediate in the biosynthesis pathway of bile acid. Recently, 27-OHC was reported to cause inflammation and apoptosis in various types of cells. The aim of this study was to assess the production of 27-OHC in the airways of patients with COPD and to elucidate the possible role of 27-OHC in the tissue fibrosis of COPD.
  
  
  METHODS
  Lung tissues were obtained from six control subjects and six patients with COPD, and sputum samples were obtained from 11 healthy subjects and 15 patients with COPD. The expression of sterol 27-hydroxylase in the lung was investigated by immunohistochemistry. The amounts of 27-OHC in the sputum were quantified by the liquid chromatography-tandem mass spectrometry method. Because peribronchial fibrosis in peripheral airways is involved in the airflow limitation of COPD, we investigated the profibrotic effects of 27-OHC in vitro.
  
  
  RESULTS
  The expression of sterol 27-hydroxylase was significantly enhanced in the lung tissues of patients with COPD compared with control subjects. The amounts of 27-OHC in the sputum were significantly increased in the patients with COPD (P < .01), and the degree of 27-OHC production was negatively correlated with lung function (P < .01). 27-OHC augmented the differentiation of lung fibroblasts into myofibroblasts and the production of extracellular matrix protein through activation of nuclear factor-κB and subsequent transforming growth factor-β(1) upregulation.
  
  
  CONCLUSIONS
  27-OHC production is enhanced in the airways of patients with COPD and might be involved in the pathogenesis of COPD.
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan. Electronic address: sugiura@wakayama-med.ac.jp.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Sugiura
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Koarai
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ichikawa
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Minakata
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Tsunahiko
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Akamatsu
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yanagisawa
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawabata
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000368:Aged; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D053493:Cholestanetriol 26-Monooxygenase / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005541:Forced Expiratory Volume; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology*; D013183:Sputum / Q000737:chemistry; D014797:Vital Capacity
chemical_list: D016326:Extracellular Matrix Proteins; D006888:Hydroxycholesterols; C076996:27-hydroxycholesterol; D053493:Cholestanetriol 26-Monooxygenase