Published ahead of print on May 18, 2006, doi:10.1164/rccm.200512-1835OC Am. J. Respir. Crit. Care Med., Volume 174, Number 4, August 2006, 393-399 A more recent version of this article appeared on August 15, 2006
Submitted on December 1, 2005 Clusterin Decreases Oxidative Stress in Lung Fibroblasts Exposed to Cigarette SmokeStefano Carnevali1,1 Section of Respiratory Diseases, Department of Oncology, Haematology and Pulmonology, University of Modena and Reggio Emilia, Modena, Italy, 2 Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy, 3 Department of Experimental Medicine, University of Parma, Parma, Italy, 4 ISPESL Research Center, University of Parma, Parma, Italy, 5 Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology of Health Sciences, University of Parma, Parma, Italy * To whom correspondence should be addressed. E-mail: fabbri.leonardo{at}unimo.it.
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 smoking, 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 kDa and 76-80 kDa) and the 76-80 kDa 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. Key words: COPD, emphysema, lung injury, inflammation, chronic bronchitis
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