4-O-methylgallic acid down-regulates endothelial adhesion molecule expression by inhibiting NF-κB-DNA-binding activity

Gwangsoo Lee, Hee Jun Na, Seung Namkoong, Ho Jeong Kwon, Sanghwa Han, Kwon Soo Ha, Young Guen Kwon, Hansoo Lee, Young Myeong Kim

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We here investigated the functional effect of 4-O-methylgallic acid (4-OMGA), a major metabolite of gallic acid abundant in red wine, on vascular inflammation and its action mechanism. 4-OMGA inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-α (TNF-α), resulting in the suppression of leukocyte adhesion to HUVECs. In addition, 4-OMGA inhibited the promoter activities of ICAM-1 and VCAM-1 and the activity of nuclear factor-κB (NF-κB) without affecting cytosolic IκB kinase (IKK) activation, inhibitor of κB (IκB) phosphorylation and degradation, and nuclear translocation of NF-κB. This compound did not alter nitric oxide (NO) generation, but inhibited reactive oxygen species (ROS) production in TNF-α-stimulated HUVECs, suggesting that NO and ROS are not involved in 4-OMGA-mediated inhibition of NF-κB activity. Moreover, 4-OMGA directly blocked the binding activity of NF-κB to its consensus DNA oligonucleotide, when pre-incubated with the nuclear extract from TNF-α-stimulated HUVECs, but not with the oligonucleotide alone. This inhibition was completely abolished by the addition of dithiothreitol. 4-OMGA exhibits an anti-inflammatory property by interfering with the formation of the NF-κB-DNA complex in the nuclei through direct and redox-sensitive interactions and may play an important role in the prevention of inflammatory responses such as the atherosclerotic process.

Original languageEnglish
Pages (from-to)143-151
Number of pages9
JournalEuropean Journal of Pharmacology
Volume551
Issue number1-3
DOIs
Publication statusPublished - 2006 Dec 3

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Down-Regulation
Human Umbilical Vein Endothelial Cells
DNA
Vascular Cell Adhesion Molecule-1
Tumor Necrosis Factor-alpha
Intercellular Adhesion Molecule-1
Oligonucleotides
Reactive Oxygen Species
Nitric Oxide
B-Form DNA
Gallic Acid
Dithiothreitol
Wine
Oxidation-Reduction
Blood Vessels
3,5-dihydroxy-4-methoxybenzoic acid
Leukocytes
Anti-Inflammatory Agents
Phosphotransferases
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Lee, Gwangsoo ; Na, Hee Jun ; Namkoong, Seung ; Jeong Kwon, Ho ; Han, Sanghwa ; Ha, Kwon Soo ; Kwon, Young Guen ; Lee, Hansoo ; Kim, Young Myeong. / 4-O-methylgallic acid down-regulates endothelial adhesion molecule expression by inhibiting NF-κB-DNA-binding activity. In: European Journal of Pharmacology. 2006 ; Vol. 551, No. 1-3. pp. 143-151.
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4-O-methylgallic acid down-regulates endothelial adhesion molecule expression by inhibiting NF-κB-DNA-binding activity. / Lee, Gwangsoo; Na, Hee Jun; Namkoong, Seung; Jeong Kwon, Ho; Han, Sanghwa; Ha, Kwon Soo; Kwon, Young Guen; Lee, Hansoo; Kim, Young Myeong.

In: European Journal of Pharmacology, Vol. 551, No. 1-3, 03.12.2006, p. 143-151.

Research output: Contribution to journalArticle

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AU - Lee, Gwangsoo

AU - Na, Hee Jun

AU - Namkoong, Seung

AU - Jeong Kwon, Ho

AU - Han, Sanghwa

AU - Ha, Kwon Soo

AU - Kwon, Young Guen

AU - Lee, Hansoo

AU - Kim, Young Myeong

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N2 - We here investigated the functional effect of 4-O-methylgallic acid (4-OMGA), a major metabolite of gallic acid abundant in red wine, on vascular inflammation and its action mechanism. 4-OMGA inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-α (TNF-α), resulting in the suppression of leukocyte adhesion to HUVECs. In addition, 4-OMGA inhibited the promoter activities of ICAM-1 and VCAM-1 and the activity of nuclear factor-κB (NF-κB) without affecting cytosolic IκB kinase (IKK) activation, inhibitor of κB (IκB) phosphorylation and degradation, and nuclear translocation of NF-κB. This compound did not alter nitric oxide (NO) generation, but inhibited reactive oxygen species (ROS) production in TNF-α-stimulated HUVECs, suggesting that NO and ROS are not involved in 4-OMGA-mediated inhibition of NF-κB activity. Moreover, 4-OMGA directly blocked the binding activity of NF-κB to its consensus DNA oligonucleotide, when pre-incubated with the nuclear extract from TNF-α-stimulated HUVECs, but not with the oligonucleotide alone. This inhibition was completely abolished by the addition of dithiothreitol. 4-OMGA exhibits an anti-inflammatory property by interfering with the formation of the NF-κB-DNA complex in the nuclei through direct and redox-sensitive interactions and may play an important role in the prevention of inflammatory responses such as the atherosclerotic process.

AB - We here investigated the functional effect of 4-O-methylgallic acid (4-OMGA), a major metabolite of gallic acid abundant in red wine, on vascular inflammation and its action mechanism. 4-OMGA inhibited the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-α (TNF-α), resulting in the suppression of leukocyte adhesion to HUVECs. In addition, 4-OMGA inhibited the promoter activities of ICAM-1 and VCAM-1 and the activity of nuclear factor-κB (NF-κB) without affecting cytosolic IκB kinase (IKK) activation, inhibitor of κB (IκB) phosphorylation and degradation, and nuclear translocation of NF-κB. This compound did not alter nitric oxide (NO) generation, but inhibited reactive oxygen species (ROS) production in TNF-α-stimulated HUVECs, suggesting that NO and ROS are not involved in 4-OMGA-mediated inhibition of NF-κB activity. Moreover, 4-OMGA directly blocked the binding activity of NF-κB to its consensus DNA oligonucleotide, when pre-incubated with the nuclear extract from TNF-α-stimulated HUVECs, but not with the oligonucleotide alone. This inhibition was completely abolished by the addition of dithiothreitol. 4-OMGA exhibits an anti-inflammatory property by interfering with the formation of the NF-κB-DNA complex in the nuclei through direct and redox-sensitive interactions and may play an important role in the prevention of inflammatory responses such as the atherosclerotic process.

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