Clusterin decreases oxidative stress in lung fibroblasts exposed to cigarette smoke.
BACKGROUND
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.


OBJECTIVE
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.


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.
Carnevali
Stefano
S
Department of Oncology, Haematology, and Pulmonology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy.
Luppi
Fabrizio
F
D'Arca
Domenico
D
Caporali
Andrea
A
Ruggieri
Maria Paola
MP
Vettori
Maria Vittoria
MV
Caglieri
Andrea
A
Astancolle
Serenella
S
Panico
Francesca
F
Davalli
Pierpaola
P
Mutti
Antonio
A
Fabbri
Leonardo M
LM
Corti
Arnaldo
A
D051152:Clusterin / Q000378:metabolism*; D017077:Culture Media, Conditioned; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008168:Lung / Q000166:cytology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances
D051152:Clusterin; D017077:Culture Media, Conditioned; D017392:Thiobarbituric Acid Reactive Substances