Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.

Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Zuyi Weng, Bodi Zhang, Shahrzad Asadi, Nikolaos Sismanopoulos, Alan Butcher, Xueyan Fu, Alexandra Katsarou-Katsari, Christina Antoniou, Theoharis C Theoharides
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
Materias:
R
Q
Acceso en línea:https://doaj.org/article/d64fcb783d6c43c7ac07226ec61045ce
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:d64fcb783d6c43c7ac07226ec61045ce
record_format dspace
spelling oai:doaj.org-article:d64fcb783d6c43c7ac07226ec61045ce2021-11-18T07:24:04ZQuercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.1932-620310.1371/journal.pone.0033805https://doaj.org/article/d64fcb783d6c43c7ac07226ec61045ce2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22470478/?tool=EBIhttps://doaj.org/toc/1932-6203Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell "stabilizer", is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD(2). Que and cromolyn also inhibit histamine, leukotrienes and PGD(2) from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption.Zuyi WengBodi ZhangShahrzad AsadiNikolaos SismanopoulosAlan ButcherXueyan FuAlexandra Katsarou-KatsariChristina AntoniouTheoharis C TheoharidesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e33805 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Zuyi Weng
Bodi Zhang
Shahrzad Asadi
Nikolaos Sismanopoulos
Alan Butcher
Xueyan Fu
Alexandra Katsarou-Katsari
Christina Antoniou
Theoharis C Theoharides
Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
description Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Contact dermatitis and photosensitivity are skin conditions that involve non-immune triggers such as substance P (SP), and do not respond to conventional treatment. Inhibition of mast cell cytokine release could be effective therapy for such diseases. Unfortunately, disodium cromoglycate (cromolyn), the only compound marketed as a mast cell "stabilizer", is not particularly effective in blocking human mast cells. Instead, flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions. Here, we first compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD(2). Que and cromolyn also inhibit histamine, leukotrienes and PGD(2) from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect. In two pilot, open-label, clinical trials, Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment. In summary, Que is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases, especially in formulations that permit more sufficient oral absorption.
format article
author Zuyi Weng
Bodi Zhang
Shahrzad Asadi
Nikolaos Sismanopoulos
Alan Butcher
Xueyan Fu
Alexandra Katsarou-Katsari
Christina Antoniou
Theoharis C Theoharides
author_facet Zuyi Weng
Bodi Zhang
Shahrzad Asadi
Nikolaos Sismanopoulos
Alan Butcher
Xueyan Fu
Alexandra Katsarou-Katsari
Christina Antoniou
Theoharis C Theoharides
author_sort Zuyi Weng
title Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
title_short Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
title_full Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
title_fullStr Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
title_full_unstemmed Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
title_sort quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/d64fcb783d6c43c7ac07226ec61045ce
work_keys_str_mv AT zuyiweng quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
AT bodizhang quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
AT shahrzadasadi quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
AT nikolaossismanopoulos quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
AT alanbutcher quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
AT xueyanfu quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
AT alexandrakatsaroukatsari quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
AT christinaantoniou quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
AT theoharisctheoharides quercetinismoreeffectivethancromolyninblockinghumanmastcellcytokinereleaseandinhibitscontactdermatitisandphotosensitivityinhumans
_version_ 1718423565248757760