title: Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets.
abstract: BACKGROUND
  Flavonoids, a large group of polyphenolic metabolites derived from plants have received a great deal of attention over the last several decades for their properties in inflammation and allergy. Quercetin, the most abundant of plant flavonoids, exerts a modulatory action at nanomolar concentrations on human basophils. As this mechanism needs to be elucidated, in this study we focused the possible signal transduction pathways which may be affected by this compound.
  
  
  METHODS
  K2-EDTA derived leukocyte buffy coats enriched in basophil granulocytes were treated with different concentrations of quercetin and triggered with anti-IgE, fMLP, the calcium ionophore A23187 and the phorbol ester PMA in different experimental conditions. Basophils were captured in a flow cytometry analysis as CD123bright/HLADRnon expressing cells and fluorescence values of the activation markers CD63-FITC or CD203c-PE were used to produce dose response curves. The same population was assayed for histamine release.
  
  
  RESULTS
  Quercetin inhibited the expression of CD63 and CD203c and the histamine release in basophils activated with anti-IgE or with the ionophore: the IC50 in the anti-IgE model was higher than in the ionophore model and the effects were more pronounced for CD63 than for CD203c. Nanomolar concentrations of quercetin were able to prime both markers expression and histamine release in the fMLP activation model while no effect of quercetin was observed when basophils were activated with PMA. The specific phosphoinositide-3 kinase (PI3K) inhibitor wortmannin exhibited the same behavior of quercetin in anti-IgE and fMLP activation, thus suggesting a role for PI3K involvement in the priming mechanism.
  
  
  CONCLUSIONS
  These results rule out a possible role of protein kinase C in the complex response of basophil to quercetin, while indirectly suggest PI3K as the major intracellular target of this compound also in human basophils.
authors.affiliation: Department of Pathology and Diagnostics, sect, General Pathology, strada Le Grazie 8, 37134 Verona, Italy. salvatore.chirumbolo@univr.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Chirumbolo
authors.forename: Marta
authors.initials: M
authors.lastname: Marzotto
authors.forename: Anita
authors.initials: A
authors.lastname: Conforti
authors.forename: Antonio
authors.initials: A
authors.lastname: Vella
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ortolani
authors.forename: Paolo
authors.initials: P
authors.lastname: Bellavite