Kruppel-like Factor 4 Regulates Endothelial Inflammation
| Autor: | Elazer R. Edelman, Zhiyong Lin, Mercedes Balcells, Anne Hamik, Sumita Sinha, Mukesh K. Jain, Jonathan P. Katz, Ajay Kumar, Robert E Gerzsten, Mark W. Feinberg |
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| Rok vydání: | 2007 |
| Předmět: |
Vasculitis
Nitric Oxide Synthase Type III Endothelium Thrombomodulin Kruppel-Like Transcription Factors Nitric Oxide Synthase Type II Biology Vascular endothelial growth inhibitor Biochemistry Endothelial activation Kruppel-Like Factor 4 Mice Cell Adhesion medicine Animals Humans Growth factor receptor inhibitor Endothelial dysfunction Blood Coagulation Molecular Biology Cells Cultured Inflammation Endothelial Cells Thrombosis Cell Biology medicine.disease Cell biology Vascular endothelial growth factor B Vascular endothelial growth factor A medicine.anatomical_structure Gene Expression Regulation Vascular endothelial growth factor C cardiovascular system Endothelium Vascular Stress Mechanical Inflammation Mediators |
| Zdroj: | Journal of Biological Chemistry. 282:13769-13779 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m700078200 |
| Popis: | The vascular endothelium plays a critical role in vascular homeostasis. Inflammatory cytokines and non-laminar blood flow induce endothelial dysfunction and confer a pro-adhesive and pro-thrombotic phenotype. Therefore, identification of factors that mediate the effects of these stimuli on endothelial function is of considerable interest. Kruppel-like factor 4 expression has been documented in endothelial cells, but a function has not been described. In this communication we describe the expression in vitro and in vivo of Kruppel-like factor 4 in human and mouse endothelial cells. Furthermore, we demonstrate that endothelial Kruppel-like factor 4 is induced by pro-inflammatory stimuli and shear stress. Overexpression of Kruppel-like factor 4 induces expression of multiple anti-inflammatory and anti-thrombotic factors including endothelial nitric-oxide synthase and thrombomodulin, whereas knockdown of Kruppellike factor 4 leads to enhancement of tumor necrosis factor alpha-induced vascular cell adhesion molecule-1 and tissue factor expression. The functional importance of Kruppel-like factor 4 is verified by demonstrating that Kruppel-like factor 4 expression markedly decreases inflammatory cell adhesion to the endothelial surface and prolongs clotting time under inflammatory states. Kruppel-like factor 4 differentially regulates the promoter activity of pro- and anti-inflammatory genes in a manner consistent with its anti-inflammatory function. These data implicate Kruppel-like factor 4 as a novel regulator of endothelial activation in response to pro-inflammatory stimuli. |
| Databáze: | OpenAIRE |
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