Function of GATA transcription factors in induction of endothelial vascular cell adhesion molecule-1 by tumor necrosis factor-α

Michihisa Umetani, Chikage Mataki, Naoko Minegishi, Masayuki Yamamoto, Takao Hamakubo, Tatsuhiko Kodama

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)917-922
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume21
Issue number6
StatePublished - 2001

Fingerprint

GATA Transcription Factors
Vascular Cell Adhesion Molecule-1
Tumor Necrosis Factor-alpha
Endothelial Cells
Proteins
Cytokines
Messenger RNA
Antisense Oligonucleotides
Electrophoretic Mobility Shift Assay

Keywords

  • Endothelial cells
  • GATA transcription factor
  • Human umbilical vein endothelial cells
  • Tumor necrosis factor-α
  • Vascular cell adhesion molecule-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Function of GATA transcription factors in induction of endothelial vascular cell adhesion molecule-1 by tumor necrosis factor-α. / Umetani, Michihisa; Mataki, Chikage; Minegishi, Naoko; Yamamoto, Masayuki; Hamakubo, Takao; Kodama, Tatsuhiko.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 21, No. 6, 2001, p. 917-922.

Research output: Contribution to journalArticle

Umetani, Michihisa ; Mataki, Chikage ; Minegishi, Naoko ; Yamamoto, Masayuki ; Hamakubo, Takao ; Kodama, Tatsuhiko. / Function of GATA transcription factors in induction of endothelial vascular cell adhesion molecule-1 by tumor necrosis factor-α. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 ; Vol. 21, No. 6. pp. 917-922.
@article{e9efd975d9104209bc841d5baa679ed1,
title = "Function of GATA transcription factors in induction of endothelial vascular cell adhesion molecule-1 by tumor necrosis factor-α",
abstract = "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.",
keywords = "Endothelial cells, GATA transcription factor, Human umbilical vein endothelial cells, Tumor necrosis factor-α, Vascular cell adhesion molecule-1",
author = "Michihisa Umetani and Chikage Mataki and Naoko Minegishi and Masayuki Yamamoto and Takao Hamakubo and Tatsuhiko Kodama",
year = "2001",
language = "English (US)",
volume = "21",
pages = "917--922",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

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

UR - http://www.scopus.com/inward/record.url?scp=0035718359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035718359&partnerID=8YFLogxK

M3 - Article

VL - 21

SP - 917

EP - 922

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 6

ER -