Background: Flavonoids, such as quercetin, were reported to inhibit histamine release and cytokine production by basophils, but there is no evidence describing their action on membrane markers and intracellular biochemical pathways. Objective: The aim of the study was to examine the effect of several quercetin doses on an in vitro human basophil activation system that evaluates up-regulation of membrane markers in response to agonists. Methods: Leukocyte buffy coats from K<sub>2</sub>-EDTA anti-coagulated blood were treated with different concentrations of quercetin and triggered with anti-IgE ("allergy model") and with N-formyl-Met-Leu-Phe (fMLP) ("inflammation model"). Basophils were captured as CD123<sup>bright</sup>/HLA-DR<sup>non-expressing</sup> cells in a flow cytometry analysis and fluorescence values of CD63-FITC, CD203c-PE and CD123-PECy5 were used to produce dose response curves. Results: Quercetin at a dose of 10 μg/ml strongly inhibited CD63 and CD203c membrane up-regulation triggered by both agonists, but it neither affected cell viability nor changed the expression of the phenotypic marker CD123. The anti-IgE model appeared highly sensitive to the effect of quercetin: a dose as low as 0.01 μg/ml was able to significantly decrease CD63 and CD203c membrane expression. In the fMLP model the dose response was different: quercetin doses from 0.01 to 0.1 μg/ml significantly increased up-regulation of membrane markers, achieving the highest effect with CD63. Conclusion: Very low doses of quercetin, within the pharmacological range, inhibit IgE-mediated membrane marker's up-regulation but prime the response to the chemotactic peptide fMLP; this stimulus specificity may have implications on the possible therapeutic action of the flavonoid in different pathologies.

Stimulus-specific regulation of CD63 and CD203c membrane expression in human basophils by the flavonoid quercetin

CHIRUMBOLO, Salvatore;CONFORTI, Anita;ORTOLANI, RICCARDO;VELLA, ANTONIO;MARZOTTO, Marta;BELLAVITE, Paolo
2010-01-01

Abstract

Background: Flavonoids, such as quercetin, were reported to inhibit histamine release and cytokine production by basophils, but there is no evidence describing their action on membrane markers and intracellular biochemical pathways. Objective: The aim of the study was to examine the effect of several quercetin doses on an in vitro human basophil activation system that evaluates up-regulation of membrane markers in response to agonists. Methods: Leukocyte buffy coats from K2-EDTA anti-coagulated blood were treated with different concentrations of quercetin and triggered with anti-IgE ("allergy model") and with N-formyl-Met-Leu-Phe (fMLP) ("inflammation model"). Basophils were captured as CD123bright/HLA-DRnon-expressing cells in a flow cytometry analysis and fluorescence values of CD63-FITC, CD203c-PE and CD123-PECy5 were used to produce dose response curves. Results: Quercetin at a dose of 10 μg/ml strongly inhibited CD63 and CD203c membrane up-regulation triggered by both agonists, but it neither affected cell viability nor changed the expression of the phenotypic marker CD123. The anti-IgE model appeared highly sensitive to the effect of quercetin: a dose as low as 0.01 μg/ml was able to significantly decrease CD63 and CD203c membrane expression. In the fMLP model the dose response was different: quercetin doses from 0.01 to 0.1 μg/ml significantly increased up-regulation of membrane markers, achieving the highest effect with CD63. Conclusion: Very low doses of quercetin, within the pharmacological range, inhibit IgE-mediated membrane marker's up-regulation but prime the response to the chemotactic peptide fMLP; this stimulus specificity may have implications on the possible therapeutic action of the flavonoid in different pathologies.
2010
Allergy; Basophil activation; CD203c; CD63; Flavonoid; Hormesis; Inflammation; Priming; Quercetin
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/339745
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