Abstract
BackgroundFlavonoids, 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.ResultsQuercetin 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.ConclusionsThese 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.
Highlights
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
Recent evidence from our laboratory has reported that sub-micromolar concentrations of quercetin, while inhibiting basophil activation marker expression in cells stimulated through an IgE-dependent pathway, are able to prime those markers in a classical non IgE-dependent activation pattern, such as using a formylated peptide as soluble agonist [20]
Basophils stimulated with anti-IgE or formylated peptide (fMLP) Figure 1 shows the dose response of the flavonoid quercetin on the expression of human basophil activation markers CD63 and CD203c following stimulation with
Summary
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. Flavonoids include a large group of low molecular weight polyphenolic secondary plant metabolites which can be found in fruits and vegetables, and plant derived beverages such as tea, wine and coffee [1,2,3] These natural compounds have been recognized to exert antioxidant [4], anti-bacterial and anti-viral activity, in addition to anti-allergic effects [5,6,7], and exert anti-inflammatory [8], anti-angiogenic, analgesic, cardiovascular-protective [9], anti-hypertensive [10], hepatoprotective [11], cytostatic, cancer preventive [12], in the rat cell line RBL-2H3 model [21], to inhibit the production of pro-inflammatory cytokines in HMC-1 mast cell line [22]. This study, in addition to representing a contribute to the comprehension of basophil biology, gives new clues about the modulatory role of this natural compound in cells of inflammation and allergy
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