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 language | English |
|---|---|
| Pages (from-to) | 1028-1038 |
| Number of pages | 11 |
| Journal | Free Radical Biology and Medicine |
| Volume | 47 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Oct 1 2009 |
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Keywords
- (-)-Epigallocatechin-3-gallate
- c-Jun NH-terminal kinase
- Free radicals
- HO
- Interleukin-13
- KU812 cells
- Nuclear factor of activated T cells
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)
Cite this
JNK-dependent NFATc1 pathway positively regulates IL-13 gene expression induced by (-)-epigallocatechin-3-gallate in human basophilic KU812 cells. / Wu, Haitao; Qi, Hang; Iwasaki, Dai; Zhu, Beiwei; Shimoishi, Yasuaki; Murata, Yoshiyuki; Nakamura, Yoshimasa.
In: Free Radical Biology and Medicine, Vol. 47, No. 7, 01.10.2009, p. 1028-1038.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - JNK-dependent NFATc1 pathway positively regulates IL-13 gene expression induced by (-)-epigallocatechin-3-gallate in human basophilic KU812 cells
AU - Wu, Haitao
AU - Qi, Hang
AU - Iwasaki, Dai
AU - Zhu, Beiwei
AU - Shimoishi, Yasuaki
AU - Murata, Yoshiyuki
AU - Nakamura, Yoshimasa
PY - 2009/10/1
Y1 - 2009/10/1
N2 - (-)-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.
AB - (-)-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.
KW - (-)-Epigallocatechin-3-gallate
KW - c-Jun NH-terminal kinase
KW - Free radicals
KW - HO
KW - Interleukin-13
KW - KU812 cells
KW - Nuclear factor of activated T cells
UR - http://www.scopus.com/inward/record.url?scp=69249215102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=69249215102&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2009.07.011
DO - 10.1016/j.freeradbiomed.2009.07.011
M3 - Article
C2 - 19607912
AN - SCOPUS:69249215102
VL - 47
SP - 1028
EP - 1038
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 7
ER -