Epigallocatechin-3-gallate inhibits mast cell degranulation, leukotriene C4 secretion, and calcium influx via mitochondrial calcium dysfunction.

The green tea polyphenol (-)-epigallocatechin-3-O-gallate (EGCG) has been shown to reduce allergic inflammatory responses in animal models, but the mechanisms involved are poorly understood. Despite the essential role for Ca(2+) influx in mediating proinflammatory mediator release from mast cells, little is known about the effects of EGCG on this response. In the present study we found that EGCG inhibited antigen-induced Ca(2+) influx and store-operated Ca(2+) entry (SOCE), the principal mode of Ca(2+) influx into mast cells. EGCG, but not (-)-epicatechin (EC), inhibited antigen-induced degranulation, leukotriene (LT) C(4) secretion, and Ca(2+) influx. EGCG also blocked SOCE without reducing Ca(2+) store emptying whereas EC did not, although it did reduce Ca(2+) store emptying. EGCG, but not EC, also evoked intracellular reactive oxygen species (ROS) production, mitochondrial membrane potential (Psi(m)) collapse, cardiolipin oxidation, and mitochondrial Ca(2+) ([Ca(2+)](m)) release. Furthermore, FCCP, a potent inducer of Psi(m) collapse, induced ROS production and [Ca(2+)](m) dysfunction and inhibited degranulation, LTC(4) secretion, Ca(2+) influx, and SOCE. These data suggest that ROS production and Psi(m) collapse are important mechanisms underlying the antiallergic effects of EGCG. These events may lead to [Ca(2+)](m) dysfunction and impair mitochondria-mediated facilitation of SOCE, thereby attenuating mast cell activation. Copyright (c) 2010 Elsevier Inc. All rights reserved.