Published ahead of print on May 18, 2006, doi:10.1164/rccm.200512-1835OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200512-1835OC
Clusterin Decreases Oxidative Stress in Lung Fibroblasts Exposed to Cigarette SmokeSection of Respiratory Diseases, Department of Oncology, Haematology, and Pulmonology, and Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena; Department of Experimental Medicine; ISPESL Research Center; Laboratory of Industrial Toxicology; and Department of Clinical Medicine, Nephrology of Health Sciences, University of Parma, Italy Correspondence and requests for reprints should be addressed to Leonardo M. Fabbri, M.D., Department of Oncology, Haematology, and Pulmonology, University of Modena & Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy. 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 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.
Key Words: chronic bronchitis • chronic obstructive pulmonary disease • emphysema • inflammation • lung injury This article has been cited by other articles:
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