Signaling pathways of the TREM-1- and TLR4-mediated neutrophil oxidative burst
| Autor: | Philipp Haselmayer, Michael Stassen, Hansjörg Schild, Helmut R. Salih, Christine Tertilt, Martin Daniel, Markus P. Radsak |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Lipopolysaccharide Neutrophils Blotting Western Cell Separation p38 Mitogen-Activated Protein Kinases chemistry.chemical_compound Phosphatidylinositol 3-Kinases Immunology and Allergy Humans Receptors Immunologic Receptor Protein kinase B Respiratory Burst Membrane Glycoproteins Phospholipase C Kinase Flow Cytometry Triggering Receptor Expressed on Myeloid Cells-1 Respiratory burst Cell biology Enzyme Activation Toll-Like Receptor 4 chemistry TLR4 Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Journal of innate immunity. 1(6) |
| ISSN: | 1662-8128 |
| Popis: | The triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in the innate inflammatory response to microbial infections. Activation and expression of TREM-1 by polymorphonuclear neutrophils (PMN) occurs in concert with Toll-like receptors (TLR) such as TLR4 for bacterial lipopolysaccharide. However, it is currently unclear how this is mediated on a molecular level. Using pharmacological inhibitors and Western blot analysis we demonstrate that phosphatidyl inositide 3-kinase, phospholipase C and the mitogen-activated kinase p38MAPK are essential for the TREM-1- and TLR4-induced oxidative burst of human PMN. The activation of protein kinase B and extracellular signal-related kinase show characteristic phosphorylation patterns upon single or co-ligation indicating individual activation pathways of both receptors. Taken together, we provide new insights into the mechanisms how TREM-1 and TLR interact creating synergistic activation in PMN. These results shed a new light on our understanding of how the innate inflammatory responses are regulated and might contribute to the development of future concepts for the treatment of severe inflammatory conditions such as sepsis. |
| Databáze: | OpenAIRE |
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