Bimodal action of the flavonoid quercetin on basophil function: An investigation of the putative biochemical targets

被引：33
作者：
Chirumbolo S. [1 ,4 ]
Marzotto M. [1 ,4 ]
Conforti A. [2 ,4 ]
Vella A. [3 ]
Ortolani R. [3 ]
Bellavite P. [1 ,4 ]
机构：
[1] Department of Pathology and Diagnostics, Sect. General Pathology, 37134 Verona
[2] Department of Medicine and Public Health-sect. Pharmacology, University of Verona
[3] Immunopathology Service, University Hospital, Policlinico GB Rossi, 37134 Verona
[4] 37134 Verona
来源：
Clinical and Molecular Allergy | / 8卷 / 1期
关键词：
Quercetin; Histamine Release; Calcium Ionophore; Human Basophil; Flavonoid Quercetin;
D O I：
10.1186/1476-7961-8-13
中图分类号：
学科分类号：
摘要：
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. © 2010 Chirumbolo et al; licensee BioMed Central Ltd.
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共 53 条
[1]  
Hertog M.G., Hollman P.C., Potential health effects of the dietary flavonol quercetin, Eur J Clin Nutr, 50, pp. 63-71, (1996)
[2]  
Hollman P.C., Katan M.B., Dietary flavonoids: intake, health effects and bioavailability, Food Chem Toxicol, 37, pp. 937-942, (1999)
[3]  
Hollman P.C., Katan M.B., Health effects and bioavailability of dietary flavonols, Free Radic Res, 31, SUPPL, (1999)
[4]  
Woodman O.L., Chan E.C., Vascular and anti-oxidant actions of flavonols and flavones, Clin Exp Pharmacol Physiol, 31, pp. 786-790, (2004)
[5]  
Kawai M., Hirano T., Higa S., Arimitsu J., Maruta M., Kuwahara Y., Ohkawara T., Hagihara K., Yamadori T., Shima Y., Ogata A., Kawase I., Tanaka T., Flavonoids and related compounds as anti-allergic substances, Allergol Int, 56, pp. 113-123, (2007)
[6]  
Jeong K.W., Lee J.Y., Kang D.I., Lee J.U., Shin S.Y., Kim Y., Screening of flavonoids as candidate antibiotics against Enterococcus faecalis, J Nat Prod, 72, pp. 719-724, (2009)
[7]  
Cushnie T.P., Lamb A.J., Antimicrobial activity of flavonoids, Int J Antimicrob Agents, 26, pp. 343-356, (2005)
[8]  
Garcia-Lafuente A., Guillamon E., Villares A., Rostagno M.A., Martinez J.A., Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease, Inflamm Res, 58, 9, pp. 537-552, (2009)
[9]  
Terao J., Kawai Y., Murota K., Vegetable flavonoids and cardiovascular disease, Asia Pac J Clin Nutr, 17, SUPPL 1, pp. 291-293, (2008)
[10]  
Perez-Vizcaino F., Duarte J., Jimenez R., Santos-Buelga C., Osuna A., Antihypertensive effects of the flavonoid quercetin, Pharmacol Rep, 61, pp. 67-75, (2009)
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