help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on June 22, 2006, doi:10.1165/rcmb.2006-0149OC

Am. J. Respir. Cell Mol. Biol., Volume 35, Number 5, November 2006, 602-610

A more recent version of this article appeared on November 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2006-0149OCv1
35/5/602    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nanua, S.
Right arrow Articles by Hershenson, M. B
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nanua, S.
Right arrow Articles by Hershenson, M. B

Submitted on April 18, 2006
Revised on June 16, 2006

Quercetin Blocks Airway Epithelial Cell Chemokine Expression

Suparna Nanua1, Suzanna M Zick2, Juan E Andrade3, John R Burgess3, Nicholas W Lukacs4, and Marc B Hershenson5*

1 Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA, 2 Department of Family Medicine, University of Michigan, Ann Arbor, MI, USA, 3 Department of Foods and Nutrition, Purdue University, West Lafayette, IN, USA, 4 Department of Pathology, University of Michigan, Ann Arbor, MI, USA, 5 Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

* To whom correspondence should be addressed. E-mail: mhershen{at}umich.edu.

Quercetin (3,3',4',5,7-pentahydroxyflavone), a dietary flavonoid, is an inhibitor of phosphatidylinositol (PI) 3-kinase and potent antioxidant. We hypothesized that quercetin blocks airway epithelial cell chemokine expression via PI 3-kinase-dependent mechanisms. Pre-treatment with quercetin and the PI 3-kinase inhibitor LY294002 each reduced tumor necrosis factor (TNF)-{alpha}-induced intereukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells. Quercetin also inhibited TNF-{alpha}-induced PI 3-kinase activity, Akt phosphorylation, intracellular H2O2 production, nuclear factor (NF)-{kappa}B transactivation, IL-8 promoter activity and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-{kappa}B transactivation via a PI 3-kinase/Akt-dependent pathway. Quercetin also reduced TNF-{alpha}-induced chemokine secretion in the presence of the transcriptional inhibitor actinomycin D, while inducing phosphorylation of eukaryotic translation initiation factor (eIF)-2{alpha}, suggesting that quercetin attenuates chemokine expression by post-transcriptional as well as transcriptional mechanisms. Finally, we tested the effects of quercetin in cockroach antigen-sensitized and challenged mice. These mice show MCP-1-dependent airways hyperresponsiveness and inflammation. Quercetin significantly reduced lung MCP-1 and methacholine responsiveness. We conclude that quercetin blocks airway cell chemokine expression via transcriptional and post-transcriptional pathways.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2006 American Thoracic Society. 		  ATS Best of the Web