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Suppression of Experimental Autoimmune Encephalomyelitis by Tyrphostin AG-556 |
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| Authors: | Talma Brenner Enrique Poradosu Dov Soffer Camille Sicsic Aviv Gazit Alexander Levitzki |
| Affiliation: | aDepartment of Neurology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, 91120;bDepartment of Biological Chemistry, Institute of Life Sciences, Department of Organic Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel;cDepartment of Pathology, Hadassah University Hospital, Hebrew University Hadassah Medical School, Jerusalem, 91120 |
| Abstract: | Tyrosine kinase blockers from the AG 126/AG-556 tyrphostin family are shown to inhibit the lipopolysaccharide (LPS)-induced production of tumor necrosis factor α (TNFα), nitric oxide (NO), and prostaglandin E2(PGE2) in primary rat astrocytes cultures. The tyrphostin AG-556 which was previously shown to be effective against sepsis in mice and dogs also show excellent efficacy in inhibiting experimental autoimmune encephalomyelitis (EAE) in mice. AG-556 does not block the activation of JNK/SAPK and of p38/HOG and therefore seems to act at a target down stream to these kinases which is activated in stress or at a target on an obligatory parallel pathway. These findings together with previous results showing inhibition of sepsis in mice and dogs suggest that protein tyrosine kinase (PTK) blockers of the AG-556 family may be considered in the management of human autoimmune disorders such as multiple sclerosis (MS). |
| Keywords: | tyrphostins experimental autoimmune encephalomyelitis multiple sclerosis tumor necrosis factor α nitric oxide |
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