Cargando…
Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets
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 conc...
Autores principales: | , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949734/ https://www.ncbi.nlm.nih.gov/pubmed/20849592 http://dx.doi.org/10.1186/1476-7961-8-13 |
_version_ | 1782187566568570880 |
---|---|
author | Chirumbolo, Salvatore Marzotto, Marta Conforti, Anita Vella, Antonio Ortolani, Riccardo Bellavite, Paolo |
author_facet | Chirumbolo, Salvatore Marzotto, Marta Conforti, Anita Vella, Antonio Ortolani, Riccardo Bellavite, Paolo |
author_sort | Chirumbolo, Salvatore |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2949734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29497342010-10-06 Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets Chirumbolo, Salvatore Marzotto, Marta Conforti, Anita Vella, Antonio Ortolani, Riccardo Bellavite, Paolo Clin Mol Allergy Research 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. BioMed Central 2010-09-17 /pmc/articles/PMC2949734/ /pubmed/20849592 http://dx.doi.org/10.1186/1476-7961-8-13 Text en Copyright ©2010 Chirumbolo et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Chirumbolo, Salvatore Marzotto, Marta Conforti, Anita Vella, Antonio Ortolani, Riccardo Bellavite, Paolo Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets |
title | Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets |
title_full | Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets |
title_fullStr | Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets |
title_full_unstemmed | Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets |
title_short | Bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets |
title_sort | bimodal action of the flavonoid quercetin on basophil function: an investigation of the putative biochemical targets |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949734/ https://www.ncbi.nlm.nih.gov/pubmed/20849592 http://dx.doi.org/10.1186/1476-7961-8-13 |
work_keys_str_mv | AT chirumbolosalvatore bimodalactionoftheflavonoidquercetinonbasophilfunctionaninvestigationoftheputativebiochemicaltargets AT marzottomarta bimodalactionoftheflavonoidquercetinonbasophilfunctionaninvestigationoftheputativebiochemicaltargets AT confortianita bimodalactionoftheflavonoidquercetinonbasophilfunctionaninvestigationoftheputativebiochemicaltargets AT vellaantonio bimodalactionoftheflavonoidquercetinonbasophilfunctionaninvestigationoftheputativebiochemicaltargets AT ortolaniriccardo bimodalactionoftheflavonoidquercetinonbasophilfunctionaninvestigationoftheputativebiochemicaltargets AT bellavitepaolo bimodalactionoftheflavonoidquercetinonbasophilfunctionaninvestigationoftheputativebiochemicaltargets |