title: Increased 25-hydroxycholesterol concentrations in the lungs of patients with chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  25-Hydroxycholesterol (25-HC) is produced from cholesterol by the enzyme cholesterol 25-hydroxylase and is associated with atherosclerosis of vessels. Recently, 25-HC was reported to cause inflammation in various types of tissues. The aim of this study was to assess the production of 25-HC in the airways and to elucidate the role of 25-HC in neutrophil infiltration in the airways of patients with chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Eleven control never-smokers, six control ex-smokers without COPD and 13 COPD patients participated in the lung tissue study. The expression of cholesterol 25-hydroxylase in the lung was investigated. Twelve control subjects and 17 patients with COPD also participated in the sputum study. The concentrations of 25-HC in sputum were quantified by liquid chromatography/mass spectrometry/mass spectrometry analysis. To elucidate the role of 25-HC in neutrophilic inflammation of the airways, the correlation between 25-HC levels and neutrophil counts in sputum was investigated.
  
  
  RESULTS
  The expression of cholesterol 25-hydroxylase was significantly enhanced in lung tissue from COPD patients compared with that from control subjects. Cholesterol 25-hydroxylase was localized in alveolar macrophages and pneumocytes of COPD patients. The concentration of 25-HC in sputum was significantly increased in COPD patients and was inversely correlated with percent of predicted forced vital capacity, forced expiratory volume in 1 s and diffusing capacity of carbon monoxide. The concentrations of 25-HC in sputum were significantly correlated with sputum interleukin-8 levels and neutrophil counts.
  
  
  CONCLUSIONS
  25-HC production was enhanced in the airways of COPD patients and may play a role in neutrophilic inflammation.
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, Wakayama, Japan. sugiura@wakayama-med.ac.jp
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Akira
authors.initials: A
authors.lastname: Koarai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Minakata
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Tsunahiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Akamatsu
authors.forename: Satoru
authors.initials: S
authors.lastname: Yanagisawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Furusawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Uno
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Satomi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000368:Aged; D056809:Alveolar Epithelial Cells / Q000737:chemistry / Q000201:enzymology; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000032:analysis / Q000378:metabolism*; D016209:Interleukin-8 / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000737:chemistry* / Q000201:enzymology / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000737:chemistry / Q000201:enzymology; D013250:Steroid Hydroxylases / Q000032:analysis
chemical_list: C508606:CXCL8 protein, human; D006888:Hydroxycholesterols; D016209:Interleukin-8; C007997:25-hydroxycholesterol; D013250:Steroid Hydroxylases; C507384:cholesterol 25-hydroxylase