Induction of Tissue Factor Production but not the Upregulation of Adhesion Molecule Expression by Ceramide in Human Vascular Endothelial Cells
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MAKOTO HIROKAWA, ATSUSHI KITABAYASHI, JUN KUROKI and AKIRA B. MIURA
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The Third Department of Internal Medicine, Akita University School of Medicine, Akita 010-8543
Binding of tumor necrosis factor-a (TNF-a) to p60 TNF-a receptor induces the activation of sphingomyelinase to generate ceramide, which in turn activates certain protein kinases and phosphatases, resulting in various TNF-a-mediated biological effects. We have investigated the role for the sphingomyelin/ceramide pathway in the TNF-a-induced upregulation of adhesion molecule expression and tissue factor production of human endothelial cells. TNF-a stimulated human umbilical vascular endothelial cells (HUVECs) to upregulate the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and HLA class I molecules in addition to the induction of procoagulant tissue factor production. C2-ceramide, a highly cell-permeable ceramide analog, was able to stimulate HUVECs to produce tissue factor activity as well as TNF-a. However, C2-ceramide did not stimulate HUVECs to upregulate the expression of VCAM-1, ICAM-1 and HLA class I molecules. These results suggest that there exist both the ceramide-dependent and -independent pathways in TNF-a signal transduction system in human vascular endothelial cells.
Key words---
human endothelial cells; TNF-a; ceramide; tissue factor; adhesion molecules
© 2000 Tohoku University Medical Press
Tohoku J. Exp. Med., 2000, 191, 167-176
Address for reprints: Makoto Hirokawa, M.D., Division of Hematology, The Third Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
e-mail: hirokawa@med.akita-u.ac.jp
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