Quercetin blocks airway epithelial cell chemokine expression

Suparna Nanua, Suzanna M. Zick, Juan E. Andrade, Umadevi S. Sajjan, John R. Burgess, Nicholas W. Lukacs, Marc B. Hershenson

Research output: Contribution to journalArticlepeer-review

Abstract

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 TNF-α-induced IL-8 and monocyte chemoattractant protein (MCP)-1 (also called CCL2) expression in cultured human airway epithelial cells. Quercetin also inhibited TNF-α-induced PI 3-kinase activity, Akt phosphorylation, intracellular H2O2 production, NF-κB transactivation, IL-8 promoter activity, and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-κB transactivation via a PI 3-kinase/Akt-dependent pathway. Quercetin also reduced TNF-α-induced chemokine secretion in the presence of the transcriptional inhibitor actinomycin D, while inducing phosphorylation of eukaryotic translation initiation factor (eIF)-2α, 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.

Original languageEnglish (US)
Pages (from-to)602-610
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume35
Issue number5
DOIs
StatePublished - Nov 2006
Externally publishedYes

Keywords

  • Asthma
  • Chemokines
  • Epithelial cells
  • Lung
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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