TY - JOUR
T1 - Increase of 27-hydroxycholesterol in the airways of patients with COPD
T2 - Possible role of 27-hydroxycholesterol in tissue fibrosis
AU - Kikuchi, Takashi
AU - Sugiura, Hisatoshi
AU - Koarai, Akira
AU - Ichikawa, Tomohiro
AU - Minakata, Yoshiaki
AU - Matsunaga, Kazuto
AU - Nakanishi, Masanori
AU - Hirano, Tsunahiko
AU - Akamatsu, Keiichirou
AU - Yanagisawa, Satoru
AU - Furukawa, Kanako
AU - Kawabata, Hiroki
AU - Ichinose, Masakazu
N1 - Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Ichinose has served on scientific advisory boards for AstraZeneca; GlaxoSmithKline KK; Nippon Boehringer Ingelheim Co, Ltd; and Novartis Pharma KK and has received unrestricted grant funding from GlaxoSmithKline KK; Nippon Boehringer Ingelheim Co, Ltd; Abbott Japan Co, Ltd; and Novartis Pharma KK. Drs Kikuchi, Sugiura, Koarai, Ichikawa, Minaka, Matsunaga, Nakanishi, Hirano, Akamatsu, Yanagisawa, Furukawa, and Kawabata have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2012/8
Y1 - 2012/8
N2 - 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- k B and subsequent transforming growth factor- β1 upregulation. Conclusions:27-OHC production is enhanced in the airways of patients with COPD and might be involved in the pathogenesis of COPD.
AB - 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- k B and subsequent transforming growth factor- β1 upregulation. Conclusions:27-OHC production is enhanced in the airways of patients with COPD and might be involved in the pathogenesis of COPD.
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U2 - 10.1378/chest.11-2091
DO - 10.1378/chest.11-2091
M3 - Article
C2 - 22281802
AN - SCOPUS:84864805188
VL - 142
SP - 329
EP - 337
JO - Diseases of the chest
JF - Diseases of the chest
SN - 0012-3692
IS - 2
ER -