Epigallocatechin gallate inhibits histamine release from rat basophilic leukemia (RBL-2H3) cells: role of tyrosine phosphorylation pathway.
Some tea polyphenolic compounds including (-)-epigallocatechin gallate (EGCG) have been shown to inhibit histamine release from mast cells through poorly understood mechanisms. By using a mast cell model rat basophilic leukemia (RBL-2H3) cells we explored the mechanism of the inhibition. EGCG inhibited histamine release from RBL-2H3 cells in response to antigen or the calcium-ionophore A23187, while (-)-epicatechin (EC) had little effect. Increased tyrosine phosphorylation of several proteins including approximately 120 kDa proteins occurred in parallel with the secretion induced by either stimulation. EGCG also inhibited tyrosine phosphorylation of the approximately 120-kDa proteins induced by either stimulation, whereas EC did not. The tyrosine kinase-specific inhibitor piceatannol inhibited the secretion and tyrosine phosphorylation of these proteins induced by either stimulation also. Further analysis showed that the focal adhesion kinase pp125(FAK) was one of the approximately 120-kDa proteins. These findings suggest that EGCG prevents histamine release from mast cells mainly by inhibiting tyrosine phosphorylation of proteins including pp125(FAK).
Department of Immunology and Microbiology, Nihon University School of Medicine, Tokyo, 173-8610, Japan.
K
K
Yamashita
Y
Y
Suzuki
T
T
Matsui
T
T
Yoshimaru
M
M
Yamaki
M
M
Suzuki-Karasaki
S
S
Hayakawa
K
K
Shimizu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism* / Q000473:pathology; D007942:Leukemia, Experimental / Q000378:metabolism* / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine
D000970:Antineoplastic Agents; D014443:Tyrosine; D002392:Catechin; C045651:epigallocatechin gallate