Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells

Background Flavonoids have a variety of activities including anti-allergic activities, and are known to inhibit histamine release from human basophils and murine mast cells. Objective The effects of luteolin, a flavone, on the immunoglobulin (Ig) E- mediated allergic mediator release from human cultured mast cells (HCMCs) w ere investigated and compared with those of baicalein and quercetin. Methods HCMCs were sensitized with IgE, and then treated with flavonoids be fore challenge with antihuman IgE. The amount of released mediators was det ermined as was mobilization of intracellular Ca2+ concentration, protein ki nase C (PKC) translocation and phosphorylation of intracellular proteins we re detected after anti-IgE stimulation. Results Luteolin, baicalein and quercetin inhibited the release of histamin e, leukotrienes (LTs), prostaglandin D-2 (PGD(2)), and granulocyte macropha ge-colony stimulating factor (GM-CSF) from HCMC in a concentration-dependen t manner. Additionally, the three flavonoids inhibited A23187-induced hista mine release. As concerns Ca2+ signalling, luteolin and quercetin inhibited Ca2+ influx strongly, although baicalein did slightly. With regard to PKC signalling, luteolin and quercetin inhibited PKC translocation and PKC acti vity strongly, although baicalein did slightly. The suppression of Ca2+ and PKC signallings might contribute to the inhibition of mediator release. Th e activation of extracellular signal-regulated kinases (ERKs) and c-Jun NH2 -terminal kinase (JNK), that were activated just before the release of LTs and PGD(2) and GM-CSF mRNA expression in IgE-mediated signal transduction e vents, were clearly suppressed by luteolin and quercetin. In contrast, the flavonoids did not affect the activation of p38 mitogen-activated protein k inase (p38 MAPK) pathway. Conclusion These results indicate that luteolin is a potent inhibitor of hu man mast cell activation through the inhibition of Ca2+ influx and PKC acti vation.