Increased 25-hydroxycholesterol concentrations in the lungs of patients with chronic obstructive pulmonary disease

Hisatoshi Sugiura, Akira Koarai, Tomohiro Ichikawa, Yoshiaki Minakata, Kazuto Matsunaga, Tsunahiko Hirano, Keiichiro Akamatsu, Satoru Yanagisawa, Makoto Furusawa, Yumiko Uno, Masashi Yamasaki, Yoshinori Satomi, Masakazu Ichinose

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23 Citations (Scopus)

Abstract

Background and 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. The expression of cholesterol 25-hydroxylase was up-regulated in the lungs of COPD patients. There was excessive production of 25-hydroxycholesterol in the airways of COPD patients and 25-hydroxycholesterol concentrations in the airways were associated with reduced lung function, elevated neutrophil counts and high IL-8 levels in sputum.

Original languageEnglish
Pages (from-to)533-540
Number of pages8
JournalRespirology
Volume17
Issue number3
DOIs
Publication statusPublished - 2012 Apr

Keywords

  • cholesterol 25-Hydroxylase
  • chronic obstructive pulmonary disease
  • interleukin-8
  • neutrophil
  • oxysterol

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Sugiura, H., Koarai, A., Ichikawa, T., Minakata, Y., Matsunaga, K., Hirano, T., Akamatsu, K., Yanagisawa, S., Furusawa, M., Uno, Y., Yamasaki, M., Satomi, Y., & Ichinose, M. (2012). Increased 25-hydroxycholesterol concentrations in the lungs of patients with chronic obstructive pulmonary disease. Respirology, 17(3), 533-540. https://doi.org/10.1111/j.1440-1843.2012.02136.x