TNF-alpha stimulation of MCP-1 expression is mediated by the Akt/PKB signal transduction pathway in vascular endothelial cells
| Autor: | Tomoyo Ohyama, Wen Ming Cao, Hitomi Imachi, Koji Murao, Makoto Sato, Jiro Takahara, Norman C.W. Wong, Toshihiko Ishida, Hiroyoshi Namihira |
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| Rok vydání: | 2000 |
| Předmět: |
Time Factors
Endothelium Biophysics Protein Serine-Threonine Kinases Vascular endothelial growth inhibitor Biochemistry Wortmannin chemistry.chemical_compound Proto-Oncogene Proteins medicine Humans Enzyme Inhibitors Phosphorylation Promoter Regions Genetic Molecular Biology Protein kinase B Cells Cultured Chemokine CCL2 Akt/PKB signaling pathway Tumor Necrosis Factor-alpha Cell Biology Cell biology Androstadienes medicine.anatomical_structure chemistry Gene Expression Regulation Cancer research Tumor necrosis factor alpha Endothelium Vascular Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 276(2) |
| ISSN: | 0006-291X |
| Popis: | MCP-1 is expressed in a variety of cell types including vascular endothelial cells following induction by different stimuli such as tumor necrosis factor (TNF)-alpha. Although TNF-alpha stimulates MCP-1 expression and secretion, the mechanism by which TNF-alpha stimulates expression of the MCP-1 gene is not known. In this study, we examine the involvement of the phosphatidylinositol-3-OH kinase (PI3-kinase)-Akt/PKB pathway. Exposure of human umbilical vein endothelial cells (HUVECs) to TNF-alpha elicited the rapid phosphorylation of Akt/PKB. In HUVECs, wortmannin, a PI3-kinase inhibitor, inhibits TNF-alpha-mediated MCP-1 secretion at a dose-dependent manner. Constitutively active form of Akt/PKB induces transcription of the MCP-1 gene, and cotransfection of dominant negative Akt/PKB suppressed the activation of the MCP-1 promoter induced by TNF-alpha. These findings show that Akt/PKB participates in the TNF-alpha induction of MCP-1 gene transcription in endothelial cells. |
| Databáze: | OpenAIRE |
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