Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells

Abstract

1 Mast cells participate in allergies, and also in immunity and inflammation by secreting proinflammatory cytokines. 2 Flavonoids are naturally occurring polyphenolic plant compounds, one group of which -the flavonols, inhibits histamine and some cytokine release from rodent basophils and mast cells. However, the effect of flavonols on proinflammatory mediator release and their possible mechanism of action in human mast cells is not well defined. 3 Human umbilical cord blood-derived cultured mast cells (hCBMCs) grown in the presence of stem cell factor (SCF) and interleukin (IL)-6 were preincubated for 15 min with the flavonols quercetin, kaempferol, myricetin and morin (0.01, 0.1, 1, 10 or 100 mM), followed by activation with anti-IgE. Secretion was quantitated for IL-6, IL-8, tumor necrosis factor-alpha (TNF-a), histamine and tryptase levels. 4 Release of IL-6, IL-8 and TNF-a was inhibited by 82-93% at 100 mM quercetin and kaempferol, and 31-70% by myricetin and morin. Tryptase release was inhibited by 79-96% at 100 mM quercetin, kampferol and myricetin, but only 39% by morin; histamine release was inhibited 52-77% by the first three flavonols, but only 28% by morin. These flavonols suppressed intracellular calcium ion elevations in a dose-response manner, with morin being the weakest; they also inhibited phosphorylation of the calcium-insensitive protein kinase C theta (PKC y). 5 Flavonol inhibition of IgE-mediated proinflammatory mediator release from hCBMCs may be due to inhibition of intracellular calcium influx and PKC y signaling. Flavonols may therefore be suitable for the treatment of allergic and inflammatory diseases.

Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract

“…It is well established that the cellular effects of KCl and capsaicin can be mediated by activation of calcium channels (Bell, 1993;Kopanitsa et al, 1995;Brosenitsch et al, 1998;Mohri et al, 2003). Our finding is in agreement with a recent study that reported an inhibitory effect of the flavonols, a class of plant polyphenols, on stimulated interleukin secretion which involved suppression of intracellular calcium levels in cultured mast cells (Kempuraj et al, 2005). However, our data provide the first evidence, to our knowledge, of Theobroma cacao extract blocking neuropeptide release from sensory neurons via a mechanism that is likely to involve inhibition of calcium channel activity.…”

“…The beneficial effects of polyphenols in cardiovascular disease have been shown to involve inhibition of key enzymes and transcription factors that are known to promote inflammation (Bode and Zigang, 2003;Yoon and Baek, 2005). Much of this research has focused on the antioxidant and radical scavenging capacity of polyphenols in immune and endothelial cells to suppress inflammation (Sanbongi et al, 1998;Stoclet et al, 1999;Kempuraj et al, 2005). Furthermore, many of the health benefits attributed to dietary polyphenols are due to their ability to repress inflammatory responses by inhibiting the production and release of cytokines and other inflammatory mediators from immune cells (Chen et al, 2002;Veronique et al, 2004;Wheeler et al, 2004).…”

Helicobacter pylori infection can modulate the susceptibility of gastric mucosa cells to MNNG

“…Additionally, quercetin might exert an anti-inflammatory effect by negatively modulating pro-inflammatory factors, such as interleukine 6, interleukine 8 and TNF-alpha, inhibiting the formation of the inflammatory mediators prostaglandins and leukotrienes, and histamine release. [15,16]. Our results showed that at high concetrations, quercetin induced DNA damage in PBLs, and this effect might be associated with the absence or a low level of potential prooxidative factors and reactive oxygen species in the reaction enviroment.…”

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice

“…18 Flavonols of kaempferol and quercetin inhibit IgEmediated release of pro-inflammatory IL-6, IL-8 and TNF-a from mast cells possibly through inhibition of intracellular calcium influx and PKC theta signaling, being suitable for the treatment of allergic and inflammatory diseases. 28 Our recent studies have demonstrated that kaempferol suppresses eosionphil infiltration and airway inflammation in airway epithelial cells and in mice with allergic asthma. 20,21 The current study further investigated whether kaempferol inhibited airway fibrosis responsible for the structural remodeling of airways.…”