Quercetin blocks airway epithelial cell chemokine expression

Am J Respir Cell Mol Biol. 2006 Nov;35(5):602-10. doi: 10.1165/rcmb.2006-0149OC. Epub 2006 Jun 22.


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. Pretreatment with quercetin and the PI 3-kinase inhibitor LY294002 each reduced TNF-alpha-induced 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 H(2)O(2) production, NF-kappaB transactivation, IL-8 promoter activity, and steady-state mRNA levels, consistent with the notion that quercetin inhibits chemokine expression by attenuating NF-kappaB 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)-2alpha, 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / administration & dosage
  • Allergens / immunology
  • Animals
  • Antioxidants / metabolism
  • Bronchial Provocation Tests
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Chromones / metabolism
  • Cockroaches
  • Enzyme Inhibitors / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Female
  • Gene Expression Regulation
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Morpholines / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quercetin / metabolism*
  • Reactive Oxygen Species / metabolism
  • Respiratory Mucosa / cytology*
  • Signal Transduction / physiology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Allergens
  • Antioxidants
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Chromones
  • Enzyme Inhibitors
  • Interleukin-8
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Quercetin
  • Proto-Oncogene Proteins c-akt