Quercetin restores corticosteroid sensitivity in cells from patients with chronic obstructive pulmonary disease.

File Description SizeFormat 
Mitani A et al Exp Lung Res 2017.docxAccepted version1.04 MBMicrosoft WordView/Open
Title: Quercetin restores corticosteroid sensitivity in cells from patients with chronic obstructive pulmonary disease.
Authors: Mitani, A
Azam, A
Vuppusetty, C
Ito, K
Mercado, N
Barnes, PJ
Item Type: Journal Article
Abstract: Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Oxidative stress from cigarette smoke and chronic inflammation is likely to induce this corticosteroid insensitivity. Quercetin is a polyphenol that has been reported to be an active oxygen scavenger as well as a functional adenosine monophosphate-activated protein kinase (AMPK) activator. The aim of this study was to investigate the effect of quercetin on corticosteroid responsiveness in COPD cells. Corticosteroid sensitivity was examined in human monocytic U937 cells exposed to cigarette smoke extract (CSE) and peripheral blood mononuclear cells (PBMC) collected from patients with COPD. Corticosteroid sensitivity was determined as the dexamethasone concentration causing 40% inhibition of tumor necrosis factor alpha-induced CXCL8 production (Dex-IC40) in the presence or absence of quercetin. In U937 cells, treatment with quercetin activated AMPK and induced expression of nuclear factor erythroid 2-related factor 2, and consequently reversed CSE-induced corticosteroid insensitivity. PBMC from patients with COPD showed corticosteroid insensitivity compared with those from healthy volunteers, and treatment with quercetin restored corticosteroid sensitivity. In conclusion, quercetin restores corticosteroid sensitivity, and has the potential to be a novel treatment in combination with corticosteroids in COPD.
Issue Date: 11-Dec-2017
Date of Acceptance: 14-Oct-2017
URI: http://hdl.handle.net/10044/1/56360
DOI: http://www.tandfonline.com/10.1080/01902148.2017.1393707
ISSN: 1521-0499
Publisher: Taylor & Francis
Start Page: 417
End Page: 425
Journal / Book Title: Experimental Lung Research
Volume: 43
Issue: 9-10
Copyright Statement: This is an Accepted Manuscript of an article published by Taylor & Francis Group in Experimental Lung Research on 11 Dec 2017, available online at: http://www.tandfonline.com/10.1080/01902148.2017.1393707
Keywords: adenosine monophosphate-activated protein kinase
chronic obstructive pulmonary disease
corticosteroid sensitivity
quercetin
adenosine monophosphate-activated protein kinase
chronic obstructive pulmonary disease
corticosteroid sensitivity
quercetin
1102 Cardiovascular Medicine And Haematology
Respiratory System
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx