Clusterin decreases oxidative stress in lung fibroblasts exposed to cigarette smoke
Clusterin decreases oxidative stress in lung fibroblasts exposed to cigarette smoke
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DOI：
10.1164/rccm.200512-1835oc
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发表时间：
2006-08-15
影响因子：
24.7
通讯作者：
Corti, Arnaldo
中科院分区：
文献类型：
--
作者：
Carnevali, Stefano;Luppi, Fabrizio;Corti, Arnaldo
理由：香烟烟雾对肺成纤维细胞造成损伤，部分是通过氧化应激，氧化应激可导致各种肺部疾病，如慢性阻塞性肺疾病。Clusterin是一种广泛分布的蛋白质，具有多种功能，包括对氧化应激的细胞保护作用。目的：为了确定clusterin是否参与肺对香烟烟雾的防御，我们研究了香烟烟雾提取物对clusterin表达的影响及其对氧化应激的保护作用。将成纤维细胞与条件培养基和香烟烟雾提取物共孵育，并通过免疫组织化学分析从非吸烟者、吸烟者和戒烟者获得的支气管活检标本。在2.5%和5.0%的浓度下，香烟烟雾提取物诱导氧化应激。它还显著增加了两种丛生素亚型（60和76-80 kD）的表达，并在孵育培养基中分泌76-80 kD亚型。成纤维细胞与条件培养基共孵育显着降低了香烟烟雾提取物引起的细胞氧化。从吸烟者和戒烟者支气管活检标本的clusterin的免疫组织化学分析显示，clusterin主要定位在粘膜下层。结论：我们得出结论，clusterin可能有一个保护作用，对香烟烟雾诱导的氧化应激肺成纤维细胞。
Rationale: Cigarette smoke causes injury to lung fibroblasts, partly by means of oxidative stress, and oxidative stress can lead to various lung diseases, such as chronic obstructive pulmonary disease. Clusterin is a widely distributed protein with many functions, including cellular protection in response to oxidative stress.Objectives: To determine whether clusterin is involved in the defense of the lung against cigarette smoke, we investigated the effects of cigarette smoke extract on clusterin expression and its protective effect, if any, against oxidative stress.Methods: Fibroblasts were coincubated with conditioned medium and cigarette smoke extract, and bronchial biopsy specimens obtained from nonsmokers, smokers, and ex-smokers were analyzed by immunohistochemistry.Measurements and Main Results: At concentrations of 2.5 and 5.0%, cigarette smoke extract induced oxidative stress. It also markedly increased the expression of two clusterin isoforms (60 and 76-80 kD) and the 76-80-kD isoform was secreted in the incubation medium. Coincubation of fibroblasts with conditioned medium significantly decreased the cellular oxidation caused by the cigarette smoke extract. Immunohistochemical analysis of clusterin on bronchial biopsy specimens obtained from smokers and ex-smokers showed localization of clusterin mainly in the submucosa.Conclusions: We conclude that clusterin may have a protective effect against cigarette smoke-induced oxidative stress in lung fibroblasts.