TY - JOUR
T1 - Function of GATA transcription factors in induction of endothelial vascular cell adhesion molecule-1 by tumor necrosis factor-α
AU - Umetani, Michihisa
AU - Mataki, Chikage
AU - Minegishi, Naoko
AU - Yamamoto, Masayuki
AU - Hamakubo, Takao
AU - Kodama, Tatsuhiko
PY - 2001
Y1 - 2001
N2 - Endothelial vascular cell adhesion molecule-1 (VCAM-1) is expressed in response to cytokine stimulation and plays a critical role in inflammatory reactions. Previously, we developed a novel VCAM-1 inhibitor that acts through a mechanism independent of nuclear factor-κB activity. It suppresses the binding activity of GATA proteins in cytokine-stimulated endothelial cells, which may be related to the anti-VCAM-1 induction effect of this drug. In this study, we investigated the role of GATA proteins in the induction of VCAM-1 by tumor necrosis factor-α (TNF-α) in human endothelial cells. The mRNA expression of GATA-6 was increased, whereas GATA-3 mRNA was decreased by TNF-α stimulation. Electrophoretic mobility shift assay showed that TNF-α stimulation increased the DNA binding of GATA-6 but decreased that of GATA-3. Experiments using protein overexpression or antisense oligonucleotides revealed that GATA-6 potently acts as a positive regulator of VCAM-1 gene transcription. In contrast, overexpression of GATA-3 was able to suppress TNF-α-induced VCAM-1 expression. Our results provide evidence of the importance of GATA proteins in the induction of VCAM-1 by TNF-α in vascular endothelial cells. The switch from GATA-3 to GATA-6 is taken to be an important transcriptional control event in TNF-α induction of VCAM-1.
AB - Endothelial vascular cell adhesion molecule-1 (VCAM-1) is expressed in response to cytokine stimulation and plays a critical role in inflammatory reactions. Previously, we developed a novel VCAM-1 inhibitor that acts through a mechanism independent of nuclear factor-κB activity. It suppresses the binding activity of GATA proteins in cytokine-stimulated endothelial cells, which may be related to the anti-VCAM-1 induction effect of this drug. In this study, we investigated the role of GATA proteins in the induction of VCAM-1 by tumor necrosis factor-α (TNF-α) in human endothelial cells. The mRNA expression of GATA-6 was increased, whereas GATA-3 mRNA was decreased by TNF-α stimulation. Electrophoretic mobility shift assay showed that TNF-α stimulation increased the DNA binding of GATA-6 but decreased that of GATA-3. Experiments using protein overexpression or antisense oligonucleotides revealed that GATA-6 potently acts as a positive regulator of VCAM-1 gene transcription. In contrast, overexpression of GATA-3 was able to suppress TNF-α-induced VCAM-1 expression. Our results provide evidence of the importance of GATA proteins in the induction of VCAM-1 by TNF-α in vascular endothelial cells. The switch from GATA-3 to GATA-6 is taken to be an important transcriptional control event in TNF-α induction of VCAM-1.
KW - Endothelial cells
KW - GATA transcription factor
KW - Human umbilical vein endothelial cells
KW - Tumor necrosis factor-α
KW - Vascular cell adhesion molecule-1
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U2 - 10.1161/01.ATV.21.6.917
DO - 10.1161/01.ATV.21.6.917
M3 - Article
C2 - 11397697
AN - SCOPUS:0035718359
SN - 1079-5642
VL - 21
SP - 917
EP - 922
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 6
ER -