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JNK-dependent NFATc1 pathway positively regulates IL-13 gene expression induced by (-)-epigallocatechin-3-gallate in human basophilic KU812 cells.
- Source :
-
Free radical biology & medicine [Free Radic Biol Med] 2009 Oct 01; Vol. 47 (7), pp. 1028-38. Date of Electronic Publication: 2009 Jul 14. - Publication Year :
- 2009
-
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.
- Subjects :
- Anthracenes pharmacology
Basophils metabolism
Catechin pharmacology
Cell Line
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Humans
Hydrogen Peroxide metabolism
Interleukin-13 biosynthesis
JNK Mitogen-Activated Protein Kinases antagonists & inhibitors
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
Basophils drug effects
Catechin analogs & derivatives
Gene Expression drug effects
Interleukin-13 genetics
JNK Mitogen-Activated Protein Kinases metabolism
NFATC Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4596
- Volume :
- 47
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Free radical biology & medicine
- Publication Type :
- Academic Journal
- Accession number :
- 19607912
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2009.07.011