Signal transduction pathways in mast cell granule-mediated endothelial cell activation
| Autor: | Kottarappat N. Dileepan, Irina V. Smirnova, Daniel J. Stechschulte, Luqi Chi, Lisa Stehno-Bittel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Umbilical Veins MAP Kinase Signaling System Immunology Lipopolysaccharide Biology Cytoplasmic Granules Calcium in biology Rats Sprague-Dawley chemistry.chemical_compound medicine lcsh:Pathology Animals Humans Mitogen-Activated Protein Kinase 8 Calcium Signaling Mast Cells Kinase activity Phosphorylation Cells Cultured Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Interleukin-6 Mast cell granule Serine Endopeptidases Degranulation NF-kappa B Cell Biology Mast cell Cell biology Rats Endothelial stem cell Serine protease medicine.anatomical_structure chemistry Endothelial cells Endothelium Vascular Signal transduction Mitogen-Activated Protein Kinases Histamine lcsh:RB1-214 Research Article |
| Zdroj: | Mediators of Inflammation Mediators of Inflammation, Vol 12, Iss 2, Pp 79-87 (2003) |
| ISSN: | 0962-9351 |
| Popis: | Background:We have previously shown that incubation of human endothelial cells with mast cell granules results in potentiation of lipopolysaccharide-induced production of interleukin-6 and interleukin-8.Aims:The objective of the present study was to identify candidate molecules and signal transduction pathways involved in the synergy between mast cell granules and lipopolysaccharide on endothelial cell activation.Methods:Human umbilical vein endothelial cells were incubated with rat mast cell granules in the presence and absence of lipopolysaccharide, and IL-6 production was quantified. The status of c-Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2 activation, nuclear factor-κB translocation and intracellular calcium levels were determined to identify the mechanism of synergy between mast cell granules and lipopolysaccaride.Results:Mast cell granules induced low levels of interleukin-6 production by endothelial cells, and this effect was markedly enhanced by lipopolysaccharide. The results revealed that both serine proteases and histamine present in mast cell granules were involved in this activation process. Mast cell granules increased intracellular calcium, and activated c-Jun amino-terminal kinase and extracellular signal-regulated kinase 1/2. The combination of lipopolysaccharide and mast cell granules prolonged c-Jun amino-terminal kinase activity beyond the duration of induction by either stimulant alone and was entirely due to active proteases. However, both proteases and histamine contributed to calcium mobilization and extracellular signal-regulated kinase 1/2 activation. The nuclear translocation of nuclear factor-κB proteins was of greater magnitude in endothelial cells treated with the combination of mast cell granules and lipopolysaccharide.Conclusions:Mast cell granule serine proteases and histamine can amplify lipopolysaccharide-induced endothelial cell activation, which involves calcium mobilization, mitogen-activated protein kinase activation and nuclear factor-κB translocation. |
| Databáze: | OpenAIRE |
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