The small GTPase RhoB regulates TNFα signaling in endothelial cells
| Autor: | Sven van Amstel, Jeffrey Kroon, Mar Fernandez-Borja, Judith A. Elias, Simon Tol |
|---|---|
| Přispěvatelé: | Landsteiner Laboratory |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Chemokine
RHOA Leukocyte adhesion molecule RHOB p38 mitogen-activated protein kinases lcsh:Medicine Human Umbilical Vein Endothelial Cells Humans Gene Silencing Interleukin 8 rhoB GTP-Binding Protein lcsh:Science Transcription factor Multidisciplinary biology Tumor Necrosis Factor-alpha lcsh:R NF-kappa B Endocytosis Cell biology Enzyme Activation Mitogen-activated protein kinase biology.protein Cancer research lcsh:Q Inflammation Mediators Mitogen-Activated Protein Kinases Research Article Signal Transduction |
| Zdroj: | PLoS ONE, Vol 8, Iss 9, p e75031 (2013) PLoS ONE, 8(9). Public Library of Science PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The inflammatory response of endothelial cells triggered by cytokines such as TNFα and IL1β plays a pivotal role in innate immunity. Upon pro-inflammatory cytokine stimulation, endothelial cells produce chemokines and cytokines that attract and activate leukocytes, and express high levels of leukocyte adhesion molecules. This process is mediated by intracellular signaling cascades triggered by activation of e.g. the TNFα receptor (TNFR) that lead to the activation of the NFκB transcription factor and of MAP kinases, which in turn activate inflammatory gene transcription. We found that the small GTPase RhoB was strongly and rapidly upregulated in primary human endothelial cells by TNFα, IL1β and LPS. We subsequently investigated the role of RhoB in the regulation of TNFR signaling in endothelial cells by silencing RhoB expression with siRNA. We provide evidence that the TNFα-induced activation of p38 MAP kinase is strongly dependent on RhoB, but not on RhoA, while JNK activation is regulated by both RhoB and RhoA. Consistent with the important role of p38 MAP kinase in inflammation, we demonstrate that loss of RhoB impairs TNFα-induced ICAM-1 expression and reduces cell production of IL6 and IL8. In addition, we show that RhoB silencing alters the intracellular traffic of TNFα after endocytosis. Since RhoB is a known regulator of the intracellular traffic of membrane receptors, our data suggest that RhoB controls TNFα signaling through the regulation of the TNFR traffic. |
| Databáze: | OpenAIRE |
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