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

Respirology (Carlton, Vic.) (2012-02-03)
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

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). 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. 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. 25-HC production was enhanced in the airways of COPD patients and may play a role in neutrophilic inflammation.

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25-Hydroxycholesterol, ≥98%