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: Takashi Kikuchi, Hisatoshi Sugiura, Akira Koarai, Tomohiro Ichikawa, Yoshiaki Minakata, Kazuto Matsunaga, Masanori Nakanishi, Tsunahiko Hirano, Keiichirou Akamatsu, Satoru Yanagisawa, Kanako Furukawa, Hiroki Kawabata, Masakazu Ichinose
• Journal: Chest (Chest) Vol. 142 Issue 2 Pg. 329-337 (Aug 2012) ISSN: 1931-3543 [Electronic] United States
• PMID: 22281802 (Publication Type: Journal Article)

Chemical References

• Extracellular Matrix Proteins
• Hydroxycholesterols
• 27-hydroxycholesterol
• Cholestanetriol 26-Monooxygenase

Topics

• Aged
• Bronchi (drug effects, metabolism, pathology)
• Case-Control Studies
• Cell Culture Techniques
• Cholestanetriol 26-Monooxygenase (metabolism)
• Extracellular Matrix Proteins (metabolism)
• Female
• Fibroblasts (drug effects, metabolism, pathology)
• Fibrosis (etiology, metabolism, pathology)
• Forced Expiratory Volume
• Humans
• Hydroxycholesterols (metabolism, pharmacology)
• Male
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (metabolism, pathology)
• Sputum (chemistry)
• Vital Capacity