O-Methylated Catechíns from Tea Leaves Inhibit Multiple Protein Kinases in Mast Cells

Mari Maeda-Yamamoto, Naoki Inagaki, Jiro Kitaura, Takao Chikumoto, Hiroharu Kawahara, Yuko Kawakami, Mitsuaki Sano, Toshio Miyase, Hirofumi Tachibana, Hiroichi Nagai, Toshiaki Kawakami

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Tea contains a variety of bioactive compounds. In this study, we show that two O-methylated catechins, (-)-epigallocatechin-3-O-(3-O-methyl) gallate and (-)-epigallocatechin-3-O-(4-O-methyl) gallate, inhibit in vivo mast cell-dependent allergic reactions more potently than their nonmethylated form, (-)-epigallocatechin-3-O-gallate. Consistent with this, these O-methylated catechins inhibit IgE/Ag-induced activation of mouse mast cells: histamine release, leukotriene release, and cytokine production and secretion were all inhibited. As a molecular basis for the catechin-mediated inhibition of mast cell activation, Lyn, Syk, and Bruton's tyrosine kinase, the protein tyrosine kinases, known to be critical for early activation events, are shown to be inhibited by the O-methylated catechins. In vitro kinase assays using purified proteins show that the O-methylated catechins can directly inhibit the above protein tyrosine kinases. These catechins inhibit IgE/Ag-induced calcium response as well as the activation of down-stream serine/threonine kinases such as Akt and c-Jun N-terminal kinase. These observations for the first time have revealed the molecular mechanisms of antiallergic effects of tea-derived catechins.

Original languageEnglish
Pages (from-to)4486-4492
Number of pages7
JournalJournal of Immunology
Volume172
Issue number7
DOIs
Publication statusPublished - Apr 1 2004

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Maeda-Yamamoto, M., Inagaki, N., Kitaura, J., Chikumoto, T., Kawahara, H., Kawakami, Y., ... Kawakami, T. (2004). O-Methylated Catechíns from Tea Leaves Inhibit Multiple Protein Kinases in Mast Cells. Journal of Immunology, 172(7), 4486-4492. https://doi.org/10.4049/jimmunol.172.7.4486