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

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dc.contributor.author Ganesan, Shyamala
dc.contributor.author Faris, Andrea N
dc.contributor.author Comstock, Adam T
dc.contributor.author Chattoraj, Sangbrita S
dc.contributor.author Chattoraj, Asamanja
dc.contributor.author Burgess, John R
dc.contributor.author Curtis, Jeffrey L
dc.contributor.author Martinez, Fernando J
dc.contributor.author Zick, Suzanna
dc.contributor.author Hershenson, Marc B
dc.contributor.author Sajjan, Uma S
dc.date.accessioned 2010-11-04T19:10:45Z
dc.date.available 2010-11-04T19:10:45Z
dc.date.issued 2010-09-28
dc.identifier http://dx.doi.org/10.1186/1465-9921-11-131
dc.identifier.uri http://hdl.handle.net/2027.42/78260
dc.description.abstract Abstract 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.
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dc.title Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression
dc.type Journal Article
dc.description.bitstreamurl http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xml
dc.description.bitstreamurl http://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdf
dc.language.rfc3066 en
dc.description.version Peer Reviewed
dc.rights.holder Ganesan et al.; licensee BioMed Central Ltd.
dc.date.updated 2010-11-04T19:10:45Z
dc.owningcollname Interdisciplinary and Peer-Reviewed
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