Membrane-Type Serine Protease-1/Matriptase Induces Interleukin-6 and -8 in Endothelial Cells by Activation of Protease-Activated Receptor-2
| Autor: | Isabell Seitz, Ilka Ott, Henk Schulz, Robert Eckl, Stefan Seidl, Albert Schömig, Hans Peter Montens, Sibylle Hess, Richard Brandl, Gabriele Busch |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
MAPK/ERK pathway
Protein Kinase C-alpha Endothelium medicine.medical_treatment Biology p38 Mitogen-Activated Protein Kinases Catalysis Monocytes medicine Humans Receptor PAR-2 Matriptase RNA Messenger Cells Cultured Protease-activated receptor 2 Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Interleukin-6 Growth factor Interleukin-8 Serine Endopeptidases NF-kappa B Endothelial Cells Interleukin Atherosclerosis Recombinant Proteins Cell biology Enzyme Activation Endothelial stem cell medicine.anatomical_structure Biochemistry biology.protein Cytokines Hepatocyte growth factor Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 27:769-775 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000258862.61067.14 |
| Popis: | Objective— The serine protease MT-SP1/matriptase plays an important role in cell migration and matrix degradation. Hepatocyte growth factor (HGF), urokinase-type plasminogen activator (uPA), and protease-activated receptor 2 (PAR-2) have been identified as in vitro substrates of MT-SP1/matriptase. Because PAR-2 is expressed in endothelial cells and contributes to inflammatory processes, we sought to investigate the effects of MT-SP1/matriptase on endothelial cytokine expression and analyzed MT-SP1/matriptase expression in vascular cells and atherosclerotic lesions. Methods and Results— In endothelial cells, recombinant MT-SP1/matriptase dose-dependently induced interleukin (IL)-8 and IL-6 mRNA and protein expression dependent on its proteolytic activity. MT-SP1/matriptase time-dependently induced phosphorylation of p38 MAPK and p42/44 MAPK. Inhibitor experiments revealed that p38 MAPK and PKCα were necessary for IL-8 induction. PAR-2 downregulation abolished and PAR-2 overexpression augmented MT-SP1/matriptase-induced IL-8 expression as evidence for PAR-2 signaling. In human atherectomies, MT-SP1/matriptase was expressed in blood cells adherent to the endothelium. Concordantly, basal MT-SP1/matriptase expression was detected in isolated monocytes. Coincubation of monocytes and endothelial cells resulted in an increased IL-8 release, which was reduced after downregulation of endothelial PAR-2 and monocytic MT-SP1/matriptase. Conclusion— MT-SP1/matriptase induces release of proinflammatory cytokines in endothelial cells through activation of PAR-2. MT-SP1/matriptase is expressed in monocytes, thus, interaction of monocytic MT-SP1/matriptase with endothelial PAR-2 may contribute to atherosclerosis. |
| Databáze: | OpenAIRE |
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