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Type: Journal article
Title: Bacterial lipopolysaccharide and tumor necrosis factor alpha synergistically increase expression of human endothelial adhesion molecules through activation of NF-kB and p38 mitogen-activated protein kinase signaling pathways
Author: Jersmann, H.
Hii, C.
Ferrante, J.
Ferrante, A.
Citation: Infection and Immunity, 2001; 69(3):1273-1279
Publisher: Amer Soc Microbiology
Issue Date: 2001
ISSN: 0019-9567
Statement of
Hubertus P. A. Jersmann, Charles S. T. Hii, Judith V. Ferrante, and Antonio Ferrante
Abstract: One of the recognized associations of bacterial infection with cardiovascular events is the activation of endothelium and upregulation of adhesion molecules. The two major proinflammatory mediators implicated in the causation of cardiovascular events, bacterial lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF), were found to cooperate to enhance the adhesive properties of endothelial cells. These caused synergistic upregulation of intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells as determined by flow cytometry analysis and enzyme-linked immunosorbent assay. This synergism was not due to TNF causing an upregulation of CD14 expression. Treatment with both LPS and TNF resulted in a marked increase in the translocation of NF-B into the nucleus. The activity of p38 mitogen-activated protein kinase was also synergistically enhanced, while the activity of c-jun N-terminal kinase was increased in an additive manner. The results demonstrate that LPS and TNF act synergistically to upregulate the expression of endothelial cell adhesion molecules, possibly by amplification of signaling pathways upstream of transcription. These findings have implications for the understanding of the acceleration of atherosclerotic events seen in low-grade infections with gram-negative organisms.
Keywords: Endothelium, Vascular; Cell Nucleus; Humans; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Lipopolysaccharides; Tumor Necrosis Factor-alpha; NF-kappa B; Cell Adhesion Molecules; Intercellular Adhesion Molecule-1; E-Selectin; Vascular Cell Adhesion Molecule-1; Cell Compartmentation; Up-Regulation; Biological Transport; Drug Synergism
Description: Copyright © 2001, American Society for Microbiology. All rights reserved.
RMID: 0020010918
DOI: 10.1128/IAI.69.3.1273-1279.2001
Appears in Collections:Paediatrics publications

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