RRC ID 19648
著者 Wu H, Qi H, Iwasaki D, Zhu B, Shimoishi Y, Murata Y, Nakamura Y.
タイトル JNK-dependent NFATc1 pathway positively regulates IL-13 gene expression induced by (-)-epigallocatechin-3-gallate in human basophilic KU812 cells.
ジャーナル Free Radic Biol Med
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 microM) 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 H(2)O(2) 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 NH(2)-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.
巻・号 47(7)
ページ 1028-38
公開日 2009-10-1
DOI 10.1016/j.freeradbiomed.2009.07.011
PII S0891-5849(09)00413-4
PMID 19607912
MeSH Anthracenes / pharmacology Basophils / drug effects* Basophils / metabolism Catechin / analogs & derivatives* Catechin / pharmacology Cell Line Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Gene Expression / drug effects* Humans Hydrogen Peroxide / metabolism Interleukin-13 / biosynthesis Interleukin-13 / genetics* JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors JNK Mitogen-Activated Protein Kinases / metabolism* NFATC Transcription Factors / metabolism* Peroxides / metabolism Phosphorylation / drug effects RNA, Messenger / drug effects RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction Structure-Activity Relationship Up-Regulation / drug effects Up-Regulation / genetics
IF 6.17
引用数 12
WOS 分野 ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 KU812(RCB0495)