Document Detail


Increase of 27-hydroxycholesterol in the airways of patients with chronic obstructive pulmonary disease: possible role of 27-hydroxycholesterol in tissue fibrosis.
MedLine Citation:
PMID:  22281802     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 is to assess the production of 27-OHC in the airways of chronic obstructive pulmonary disease (COPD) and to elucidate the possible role of 27-OHC in the tissue fibrosis of COPD. METHODS:Lung tissues were obtained from 6 control subjects and 6 COPD patients and sputum samples were obtained from 11 healthy subjects and 15 COPD patients. The expression of sterol 27-hydroxylase in the lung was investigated by immunohistochemistry. The amounts of 27-OHC in the sputum were quantified by liquid chromatography-tandem mass spectrometry method. Because peribronchial fibrosis in peripheral airways is involved in the airflow limitation of COPD, we investigated the pro-fibrotic effects of 27-OHC in vitro. RESULTS:The expression of sterol 27-hydroxylase was significantly enhanced in the lung tissues from COPD patients compared to control subjects. The amounts of 27-OHC in the sputum were significantly increased in COPD patients (p < 0.01) and the degree of 27-OHC production was negatively correlated with the lung function (p < 0.01). 27-OHC augmented the differentiation of lung fibroblasts into myofibroblasts and the production of extracellular matrix protein through activation of nuclear factor-kappa B and subsequent transforming growth factor-β(1) up-regulation. CONCLUSIONS:27-OHC production was enhanced in the airways of COPD patients 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
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-26
Journal Detail:
Title:  Chest     Volume:  -     ISSN:  1931-3543     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan.
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