The Downregulation of Mast Cell Activation Through the Suppression of the High-Affinity IgE Receptor Expression by Green Tea Catechin Egcg

Abstract

The high-affinity IgE receptor (FcɛRI) is expressed at high levels on the cell surface of basophils and mast cells and plays a key role in a series of acute and chronic human allergic reactions. Previously, we have found that a major green tea catechin, (–)-epigallocatechin-3-O-gallate (EGCG), suppresses the FcɛRI expression on the human basophilic cells. However, there is no report for the suppressive effect of EGCG on the mast cells. Herein, we examined the effect of EGCG on the FcɛRI expression of mouse bone marrow-derived mast cells (BMMC). Flow cytometric analysis showed that EGCG was able to decrease the cell-surface expression of FcɛRI after a 24-h treatment in a dose-dependent manner. Moreover, IgE/antigen-induced histamine release from BMMC was inhibited upon treatment with EGCG. This observation indicated that the reduction of histamine release was caused by the suppression of the cell-surface FcɛRI expression. FcɛRI is a tetrameric structure comprising one α chain, one β bchain, and two γ chains. The mRNA expression of all three chains in EGCG-treated BMMC were lower than nontreated cells, suggesting that the suppressive effect of EGCG on the FcɛRI expression is due to the inhibition of mRNA expression for all three FcɛRI subunit genes. Previously, we demonstrated that the reduction of extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation was involved in the downregulation of FcɛRI expression. EGCG was shown to reduce the level of ERK1/2 phosphorylation. In addition, surface plasmon resonance assay demonstrated that the cell-surface binding of EGCG to BMMC correlated with the EGCG’s ability to suppress the FcɛRI expression. These results suggested that EGCG has the ability to downregulate FcɛRI expression of mast cells and this suppressive effect may be due to the cell-surface binding activity and subsequent reduction of ERK1/2 phosphorylation.