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首页> 外文期刊>Chest: The Journal of Circulation, Respiration and Related Systems >Increase of 27-hydroxycholesterol in the airways of patients with COPD: Possible role of 27-hydroxycholesterol in tissue fibrosis
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Increase of 27-hydroxycholesterol in the airways of patients with COPD: Possible role of 27-hydroxycholesterol in tissue fibrosis

机译：COPD患者气道中27-羟基胆固醇的增加：27-羟基胆固醇在组织纤维化中的可能作用

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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- 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.
机译：背景：27-羟基胆固醇（27-OHC）是由胆固醇27-羟化酶作为胆汁酸生物合成途径的中间体从胆固醇中产生的。最近，据报道27-OHC在各种类型的细胞中引起炎症和细胞凋亡。这项研究的目的是评估COPD患者气道中27-OHC的产生，并阐明27-OHC在COPD组织纤维化中的可能作用。方法：从6名对照受试者和6名COPD患者获得肺组织，从11名健康受试者和15名COPD患者获得痰标本。通过免疫组织化学研究了固醇27-羟化酶在肺中的表达。用液相色谱-串联质谱法对痰液中27-OHC的含量进行定量。由于外周气道的支气管周围纤维化与COPD的气流受限有关，因此我们在体外研究了27-OHC的纤维化作用。结果：与对照组相比，COPD患者肺组织中固醇27-羟化酶的表达明显增加。 COPD患者的痰液中27-OHC含量显着增加（P <.01），而27-OHC产生的程度与肺功能呈负相关（P <.01）。 27-OHC通过激活核因子-κB和随后的转化生长因子-β1上调，增强了肺成纤维细胞向肌成纤维细胞的分化以及细胞外基质蛋白的产生。结论：COPD患者气道中27-OHC的产生增加，可能与COPD的发病有关。

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