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https://hdl.handle.net/2440/9140
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Type: | Journal article |
Title: | Tumor necrosis factor-α induces adhesion molecule expression through the sphingosine kinase pathway |
Other Titles: | Tumor necrosis factor-alpha induces adhesion molecule expression through the sphingosine kinase pathway |
Author: | Xia, P. Gamble, J. Rye, K.A. Wang, L. Hii, C. Cockerill, P. Khew-Goodall, Y. Bert, A. Barter, P. Vadas, M. |
Citation: | Proceedings of the National Academy of Sciences of USA, 1998; 95(24):14196-14201 |
Publisher: | National Academy of Sciences |
Issue Date: | 1998 |
ISSN: | 0027-8424 1091-6490 |
Statement of Responsibility: | Xia, Pu ; Gamble, Jennifer R. ; Rye, Kerry-anne ; Wang, Lijun ; Cockerill, Peter ; Khew-goodall, Yeesim ; Bert, Andrew G. ; Barter, Philip J. ; Vadas, Mathew A. |
Abstract: | The signaling pathways that couple tumor necrosis factor-α (TNFα) receptors to functional, especially inflammatory, responses have remained elusive. We report here that TNFα induces endothelial cell activation, as measured by the expression of adhesion protein E-selectin and vascular adhesion molecule-1, through the sphingosine kinase (SKase) signaling pathway. Treatment of human umbilical vein endothelial cells with TNFα resulted in a rapid SKase activation and sphingosine 1-phosphate (S1P) generation. S1P, but not ceramide or sphingosine, was a potent dose-dependent stimulator of adhesion protein expression. S1P was able to mimic the effect of TNFα on endothelial cells leading to extracellular signal-regulated kinases and NF-κB activation, whereas ceramide or sphingosine was not. Furthermore, N,N-dimethylsphingosine, an inhibitor of SKase, profoundly inhibited TNFα-induced extracellular signal-regulated kinases and NF-κB activation and adhesion protein expression. Thus we demonstrate that the SKase pathway through the generation of S1P is critically involved in mediating TNFα-induced endothelial cell activation. |
Keywords: | Endothelium, Vascular Umbilical Veins Cells, Cultured Humans Sphingosine Phosphotransferases (Alcohol Group Acceptor) Mitogen-Activated Protein Kinases JNK Mitogen-Activated Protein Kinases Sphingomyelins Lysophospholipids Tumor Necrosis Factor-alpha NF-kappa B E-Selectin Vascular Cell Adhesion Molecule-1 Signal Transduction Gene Expression Regulation Enzyme Activation Kinetics Calcium-Calmodulin-Dependent Protein Kinases |
Rights: | Copyright © 1998, The National Academy of Sciences |
DOI: | 10.1073/pnas.95.24.14196 |
Published version: | http://dx.doi.org/10.1073/pnas.95.24.14196 |
Appears in Collections: | Aurora harvest Medicine publications |
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