title: Induction of tissue factor production but not the upregulation of adhesion molecule expression by ceramide in human vascular endothelial cells.
abstract: Binding of tumor necrosis factor-alpha (TNF-alpha) to p60 TNF-alpha receptor induces the activation of sphingomyelinase to generate ceramide, which in turn activates certain protein kinases and phosphatases, resulting in various TNF-alpha-mediated biological effects. We have investigated the role for the sphingomyelin/ceramide pathway in the TNF-alpha-induced upregulation of adhesion molecule expression and tissue factor production of human endothelial cells. TNF-alpha 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-alpha. 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-alpha signal transduction system in human vascular endothelial cells.
authors.affiliation: The Third Department of Internal Medicine, Akita University School of Medicine, Japan. hirokawa@med.akita-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Hirokawa
authors.forename: A
authors.initials: A
authors.lastname: Kitabayashi
authors.forename: J
authors.initials: J
authors.lastname: Kuroki
authors.forename: A B
authors.initials: AB
authors.lastname: Miura
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D020298:U937 Cells; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; C064769:N-acetylsphingosine; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine