Carnevali Stefano, Luppi Fabrizio, D'Arca Domenico, Caporali Andrea, Ruggieri Maria Paola, Vettori Maria Vittoria, Caglieri Andrea, Astancolle Serenella, Panico Francesca, Davalli Pierpaola, Mutti Antonio, Fabbri Leonardo M, Corti Arnaldo
Department of Oncology, Haematology, and Pulmonology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy.
Am J Respir Crit Care Med. 2006 Aug 15;174(4):393-9. doi: 10.1164/rccm.200512-1835OC. Epub 2006 May 18.
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.
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.
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.
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.
We conclude that clusterin may have a protective effect against cigarette smoke-induced oxidative stress in lung fibroblasts.
香烟烟雾会对肺成纤维细胞造成损伤，部分是通过氧化应激实现的，而氧化应激会导致多种肺部疾病，如慢性阻塞性肺疾病。簇集蛋白是一种广泛分布且具有多种功能的蛋白质，包括对氧化应激的细胞保护作用。
为了确定簇集蛋白是否参与肺部对香烟烟雾的防御，我们研究了香烟烟雾提取物对簇集蛋白表达的影响及其对氧化应激的保护作用（如果有的话）。
将成纤维细胞与条件培养基和香烟烟雾提取物共同孵育，并通过免疫组织化学分析从不吸烟者、吸烟者和戒烟者获取的支气管活检标本。
在浓度为2.5%和5.0%时，香烟烟雾提取物会诱导氧化应激。它还显著增加了两种簇集蛋白异构体（60和76 - 80 kD）的表达，并且76 - 80 kD异构体分泌到了孵育培养基中。成纤维细胞与条件培养基共同孵育显著降低了香烟烟雾提取物引起的细胞氧化。对吸烟者和戒烟者的支气管活检标本进行的簇集蛋白免疫组织化学分析显示，簇集蛋白主要定位于黏膜下层。
我们得出结论，簇集蛋白可能对香烟烟雾诱导的肺成纤维细胞氧化应激具有保护作用。
