Abstract
Chronic obstructive pulmonary disease is characterized by persistent and modified inflammatory responses in lung. Human sirtuin, an antiaging and antiinflammatory protein, is a metabolic NAD(+)-dependent protein/histone deacetylase that regulates proinflammatory mediators by deacetylating histone and nonhistone proteins. The aim of our study was to compare the expression of sirtuin in large and small airways in nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease. A total of 12 nonsmokers, 14 asymptomatic smokers, and 12 smokers with moderate chronic obstructive pulmonary disease were enrolled into the study. Immunohistochemical and Western blot methods were used to analyze sirtuin expression in the airways. The obtained results showed the nonuniform sirtuin expression throughout the bronchial tree. Smokers both with and without chronic obstructive pulmonary disease had decreased sirtuin expression in large airways. However, in small airways, sirtuin expression was decreased only in patients with chronic obstructive pulmonary disease. In addition, a correlation between airflow limitation, smoked pack-years and the number of sirtuin-positive cells in airways was found. Smoking is characterized by suppressed sirtuin expression in large airways, whereas chronic obstructive pulmonary disease is characterized by more severe suppression of sirtuin expression both in large and small airways.
Highlights
Chronic obstructive pulmonary disease (COPD) is characterized by a slowly progressive and irreversible obstruction of the airways
Smoking is characterized by suppressed sirtuin expression in large airways, whereas chronic obstructive pulmonary disease is characterized by more severe suppression of sirtuin expression both in large and small airways
The lung tissue specimens for the evaluation of small airways were taken from the subpleural parenchyma, but for the evaluation of large airways, the bronchial rings were taken from the segmental bronchus of the lobe obtained at surgery as far away as possible from the tumor site
Summary
Chronic obstructive pulmonary disease (COPD) is characterized by a slowly progressive and irreversible obstruction of the airways. Practically all the smokers develop chronic bronchitis characterized by inflammation in the large airways. Sirtuins (SIRTs) belong to class III histone/protein deacetylases (HDACs) and are members of the silent information regulator 2 (Sir2) family. Unlike class I and II HDACs, which consume a water molecule for direct hydrolysis of the acetyl group, sirtuins require NAD as a cosubstrate for the deacetylation reaction [2]. Gene silencing by this family of enzymes has been correlated directly with a longer lifespan [2]. Sirt is the human homologue of sir and appears to be involved in several physiological functions in-
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