Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

• Published in: Respiratory research Vol. 11; no. 1; p. 131
• Main Authors: Ganesan, Shyamala, Faris, Andrea N, Comstock, Adam T, Chattoraj, Sangbrita S, Chattoraj, Asamanja, Burgess, John R, Curtis, Jeffrey L, Martinez, Fernando J, Zick, Suzanna, Hershenson, Marc B, Sajjan, Uma S
• Format: Journal Article
• Language: English
• Published: London BioMed Central 28.09.2010; BioMed Central Ltd; Nature Publishing Group; BMC
• Subjects: Animals; Anti-inflammatory agents; Antioxidants; Antioxidants (Nutrients); Binding sites; Bronchitis; Care and treatment; Cells, Cultured; Chronic obstructive pulmonary disease; Development and progression; Disease; Disease Progression; Elastases; Experiments; Flavonoids; Free radicals; Gene Expression Regulation, Enzymologic - drug effects; Genetic aspects; Health aspects; Human subjects; Inflammation; Lipopolysaccharides - toxicity; Lung diseases; Lung diseases, Obstructive; Lungs; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - biosynthesis; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mucins; Nitric oxide; Occupational safety and health; Oxidative stress; Pancreatic Elastase - toxicity; Peroxidation; Physiological aspects; Pneumology/Respiratory System; Prevention; Propylene; Propylene glycol; Proteases; Proteins; Pulmonary Disease, Chronic Obstructive - chemically induced; Pulmonary Disease, Chronic Obstructive - enzymology; Pulmonary Disease, Chronic Obstructive - prevention & control; Quercetin; Quercetin - pharmacology; Quercetin - therapeutic use; Respiratory function; Rodents; Studies; Swine; United States; Chronic Obstructive Pulmonary Disease; Alveolar Macrophage; Elastic Recoil; Chronic Obstructive Pulmonary Disease Patient; Quercetin
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/1465-9921-11-131

Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro , while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.