Inhibition of 5-lipoxygenase blocks IL-1 beta-induced vascular adhesion molecule-1 gene expression in human endothelial cells

Inflammation is characterized by the recruitment of leukocytes and their subsequent migration from the vasculature into the tissue, where they often cause severe damage. Endothelial cells play a major role in this cascade by expressing cell surface adhesion molecules, such as VCAM-1 and ICAM-1, and...

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Veröffentlicht in:The Journal of immunology (1950) 1997-04, Vol.158 (7), p.3401-3407
Hauptverfasser: Lee, S, Felts, KA, Parry, GC, Armacost, LM, Cobb, RR
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container_end_page 3407
container_issue 7
container_start_page 3401
container_title The Journal of immunology (1950)
container_volume 158
creator Lee, S
Felts, KA
Parry, GC
Armacost, LM
Cobb, RR
description Inflammation is characterized by the recruitment of leukocytes and their subsequent migration from the vasculature into the tissue, where they often cause severe damage. Endothelial cells play a major role in this cascade by expressing cell surface adhesion molecules, such as VCAM-1 and ICAM-1, and chemokines, in response to cytokines. Many of these genes are under the control of inflammatory response transcription factors such as nuclear factor (NF)-kappa B. In this study, we examined the effects of 5-lipoxygenase inhibitors (nordihydroguaiaretic acid and AA861) on IL-1 beta-induced VCAM-1 gene expression in HUVECs. We demonstrated that 5-lipoxygenase inhibitors, but not cyclooxygenase inhibitors, block IL-1 beta-induced VCAM-1 cell surface expression and promoter activity. In transiently transfected HUVECs, NF-kappa B-dependent gene expression was inhibited by 5-lipoxygenase inhibitors. These inhibitors did not block IL-1 beta-induced nuclear translocation of NF-kappa B, inhibitor of kappa B-alpha proteolytic degradation, or significantly reduce phosphorylation of p65. These studies indicate that inhibition of 5-lipoxygenase blocks cytokine-induced VCAM-1 gene expression by reducing the functional activity of NF-kappa B/Rel proteins in HUVECs.
doi_str_mv 10.4049/jimmunol.158.7.3401
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subjects Benzoquinones - pharmacology
Biological Transport - drug effects
Cell Nucleus - drug effects
Cell Nucleus - genetics
Cells, Cultured
Endothelium, Vascular - cytology
Endothelium, Vascular - immunology
Endothelium, Vascular - metabolism
Gene Expression Regulation - drug effects
Humans
Interleukin-1 - pharmacology
Lipoxygenase Inhibitors - pharmacology
Masoprocol - pharmacology
NF-kappa B - antagonists & inhibitors
NF-kappa B - metabolism
Phosphorylation - drug effects
Promoter Regions, Genetic - drug effects
Transcription, Genetic - drug effects
Vascular Cell Adhesion Molecule-1 - biosynthesis
Vascular Cell Adhesion Molecule-1 - drug effects
Vascular Cell Adhesion Molecule-1 - genetics
title Inhibition of 5-lipoxygenase blocks IL-1 beta-induced vascular adhesion molecule-1 gene expression in human endothelial cells
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