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Thromb Haemost 2001; 85(01): 171-176
DOI: 10.1055/s-0037-1612921
Review Article
Schattauer GmbH

Expression of Vascular Endothelial Growth Factor in Human Monocyte/Macrophages Stimulated with Lipopolysaccharide

Hiroyuki Itaya
1   Department of Vascular Biology, Institute of Brain Science, and The First Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan
,
Tadaatsu Imaizumi
1   Department of Vascular Biology, Institute of Brain Science, and The First Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan
,
Hidemi Yoshida
1   Department of Vascular Biology, Institute of Brain Science, and The First Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan
,
Masayuki Koyama
2   The First Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan
,
Sohei Suzuki
2   The First Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan
,
Kei Satoh
1   Department of Vascular Biology, Institute of Brain Science, and The First Department of Surgery, Hirosaki University School of Medicine, Hirosaki, Japan
› Author Affiliations
Further Information

Publication History

Received 25 April 2000

Accepted after revision 11 August 2000

Publication Date:
08 December 2017 (online)

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Summary

Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human macrophages in response to lipopolysaccharide (LPS). Macrophages stimulated with LPS expressed VEGF mRNA and protein in concentration- and time-dependent manners. The LPS-induced expression of VEGF was inhibited by cycloheximide pretreatment, which suggested that synthesis of certain factor(s) is required for the LPS activity. The induction of VEGF was also suppressed by SB203580, an inhibitor of p38 mitogen-activated protein (MAP) kinase. These results suggest that the LPS-induced VEGF expression depends on the p38-mediated expression of c-Jun, which constitutes the AP-1 complex and binds to the AP-1 site in the VEGF promoter. Pretreatment of the cells with dexamethasone did not affect the LPS-induced upregulation of VEGF mRNA but strongly inhibited VEGF protein production, and the involvement of posttranscriptional regulation on VEGF expression by dexamethasone was suggested. The conditioned medium of LPS-stimulated macrophages enhanced the growth of cultured endothelial cells and it was inhibited by an antibody against VEGF. We conclude that macrophages produce VEGF in response to the stimulation with LPS, which may be partly mediated by the p38 MAP kinase pathway.

Keywords

Vascular endothelial growth factor - human macrophages - lipopolysaccharide - p38 MAP kinase - c-jun - AP-1
 

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