The Oxazolidinone Derivative Locostatin Induces Cytokine Appeasement1
| Autor: | Ménoret, Antoine, McAleer, Jeremy P., Ngoi, Soo-Mun, Ray, Swagatam, Eddy, Nicholas A., Fenteany, Gabriel, Lee, Seung-Joo, Rossi, Robert J., Mukherji, Bijay, Allen, David L., Chakraborty, Nitya G., Vella, Anthony T. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Clonal Anergy
Proteomics Tumor Necrosis Factor-alpha T-Lymphocytes Blotting Western Anti-Inflammatory Agents Fluorescent Antibody Technique Mice Transgenic Phosphatidylethanolamine Binding Protein Flow Cytometry Lymphocyte Activation Article Mice Inbred C57BL Mice Tandem Mass Spectrometry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Animals Cytokines Humans Electrophoresis Polyacrylamide Gel Phosphorylation Extracellular Signal-Regulated MAP Kinases Oxazolidinones Chromatography Liquid |
| Popis: | Damaging inflammation arising from autoimmune pathology and septic responses results in severe cases of disease. In both instances, anti-inflammatory compounds are used to limit the excessive or deregulated cytokine responses. We used a model of robust T cell stimulation to identify new proteins involved in triggering a cytokine storm. A comparative proteomic mining approach revealed the differential mapping of Raf kinase inhibitory protein after T cell recall in vivo. Treatment with locostatin, an Raf kinase inhibitory protein inhibitor, induced T cell anergy by blocking cytokine production after Ag recall. This was associated with a reduction in Erk phosphorylation. Importantly, in vivo treatment with locostatin profoundly inhibited TNF-alpha production upon triggering the Ag-specific T cells. This effect was not limited to a murine model because locostatin efficiently inhibited cytokine secretion by human lymphocytes. Therefore, locostatin should be a useful therapeutic to control inflammation, sepsis, and autoimmune diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|