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.
Inoue
Toshio
T
Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, Tokyo, Japan.
Suzuki
Yoshihiro
Y
Ra
Chisei
C
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D017997:Leukotriene C4; D002392:Catechin; C045651:epigallocatechin gallate; D002118:Calcium