Epigallocatechin-3-gallate inhibits mast cell degranulation, leukotriene C(4) secretion and calcium influx via mitochondrial calcium dysfunction.

Free Radic Biol Med. 2010 May 24.

Epigallocatechin-3-gallate inhibits mast cell degranulation, leukotriene C(4) secretion and calcium influx via mitochondrial calcium dysfunction.
Inoue T, Suzuki Y, Ra C.

Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, Tokyo, Japan.

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 (DeltaPsi(m)) collapse, cardiolipin oxidation and mitochondrial Ca(2+) ([Ca(2+)](m)) release. Furthermore, FCCP, a potent inducer of DeltaPsi(m) collapse, induced ROS production, [Ca(2+)](m) dysfunction and inhibited degranulation, LTC(4) secretion, Ca(2+) influx and SOCE. These data suggest that ROS production and DeltaPsi(m) collapse are important mechanisms underlying the anti-allergic 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 2010. Published by Elsevier Inc.