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

Abstract

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) were investigated and compared with those of baicalein and quercetin. Methods: HCMCs were sensitized with IgE, and then treated with flavonoids before challenge with antihuman IgE. The amount of released mediators was determined as was mobilization of intracellular Ca 2+ concentration, protein kinase C (PKC) translocation and phosphorylation of intracellular proteins were detected after anti‐IgE stimulation. Results: Luteolin, baicalein and quercetin inhibited the release of histamine, leukotrienes (LTs), prostaglandin D 2 (PGD 2), and granulocyte macrophage‐colony stimulating factor (GM‐CSF) from HCMC in a concentration‐dependent manner. Additionally, the three flavonoids inhibited A23187‐induced histamine release. As concerns Ca 2+ signalling, luteolin and quercetin inhibited Ca 2+ influx strongly, although baicalein did slightly. With regard to PKC signalling, luteolin and quercetin inhibited PKC translocation and PKC activity strongly, although baicalein did slightly. The suppression of Ca 2+ and PKC signallings might contribute to the inhibition of mediator release. The 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 events, were clearly suppressed by luteolin and quercetin. In contrast, the flavonoids did not affect the activation of p38 mitogen‐activated protein kinase (p38 MAPK) pathway. Conclusion: These results indicate that luteolin is a potent inhibitor of human mast cell activation through the inhibition of Ca 2+ influx and PKC activation.