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.
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: Behzad Yeganeh; Emilia Wiechec; Sudharsana R Ande; Pawan Sharma; Adel Rezaei Moghadam; Martin Post; Darren H Freed; Mohammad Hashemi; Shahla Shojaei; Amir A Zeki; Saeid Ghavami Journal: Pharmacol Ther Date: 2014-02-26 Impact factor: 12.310
Authors: Mariola Kurowska-Stolarska; Manhl K Hasoo; David J Welsh; Lynn Stewart; Donna McIntyre; Brian E Morton; Steven Johnstone; Ashley M Miller; Darren L Asquith; Neal L Millar; Ann B Millar; Carol A Feghali-Bostwick; Nikhil Hirani; Peter J Crick; Yuqin Wang; William J Griffiths; Iain B McInnes; Charles McSharry Journal: J Allergy Clin Immunol Date: 2016-10-14 Impact factor: 10.793
Authors: Jie Jia; Thomas M Conlon; Rim Sj Sarker; Demet Taşdemir; Natalia F Smirnova; Barkha Srivastava; Stijn E Verleden; Gizem Güneş; Xiao Wu; Cornelia Prehn; Jiaqi Gao; Katharina Heinzelmann; Jutta Lintelmann; Martin Irmler; Stefan Pfeiffer; Michael Schloter; Ralf Zimmermann; Martin Hrabé de Angelis; Johannes Beckers; Jerzy Adamski; Hasan Bayram; Oliver Eickelberg; Ali Önder Yildirim Journal: EMBO Mol Med Date: 2018-05 Impact factor: 12.137