The Oxazolidinone Derivative Locostatin Induces Cytokine Appeasement
| Autor: | Antoine Ménoret, David L. Allen, Nicholas A. Eddy, Seung-Joo Lee, Soo-Mun Ngoi, Nitya G. Chakraborty, Gabriel Fenteany, Bijay Mukherji, Robert J. Rossi, Swagatam Ray, Anthony T. Vella, Jeremy P. McAleer |
|---|---|
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 183:7489-7496 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.0901414 |
| 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-α 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: |
|