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

Abstract

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 (∆Ψ m) collapse, cardiolipin oxidation, and mitochondrial Ca 2+ ([Ca 2+] m) release. Furthermore, FCCP, a potent inducer of ∆Ψ 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 ∆Ψ 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.