JNK-dependent NFATc1 pathway positively regulates IL-13 gene expression induced by (-)-epigallocatechin-3-gallate in human basophilic KU812 cells

Haitao Wu, Hang Qi, Dai Iwasaki, Beiwei Zhu, Yasuaki Shimoishi, Yoshiyuki Murata, Yoshimasa Nakamura

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) has been reported to possess a wide range of biological and pharmacological properties. In this study, we investigated the effects of EGCG on IL-13 gene expression in human basophilic KU812 cells. The IL-13 mRNA expression level was dose-dependently increased by treatment with EGCG (5-20 μM) for 1 h and additional incubation in a medium for 23 h. EGCG significantly increased the intracellular peroxide level as detected by the peroxide-sensitive probe 2′,7′-dichlorodihydrofluorescein diacetate. A pharmacological experiment using catalase and a structure-activity relationship study revealed that the exogenously produced H2O2 significantly, but partially, contributed to the IL-13 expression as well as the intracellular oxidative status. Furthermore, EGCG at the concentration required for IL-13 up-regulation activated c-Jun NH2-terminal kinase (JNK), but not extracellular signal-regulated protein kinase or p38 mitogen-activated protein kinase in KU812 cells. Transfection of a JNK-specific siRNA as well as treatment with a JNK-specific inhibitor, SP600125, significantly reduced the EGCG-induced IL-13 mRNA expression, by 47.1 and 44.6%, respectively. In addition, we observed the nuclear translocation, mRNA up-regulation, and activation of DNA binding with the IL-13 promoter of nuclear factor of activated T cells (NFATc1) in the EGCG-treated cells. These data provide biological evidence that EGCG induces IL-13 mRNA expression via the JNK-dependent NFATc1 pathway in KU812 cells.

Original languageEnglish
Pages (from-to)1028-1038
Number of pages11
JournalFree Radical Biology and Medicine
Volume47
Issue number7
DOIs
Publication statusPublished - Oct 1 2009

Keywords

  • (-)-Epigallocatechin-3-gallate
  • Free radicals
  • HO
  • Interleukin-13
  • KU812 cells
  • Nuclear factor of activated T cells
  • c-Jun NH-terminal kinase

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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