Kontrola finalnog stadijuma imunski posredovanog dijabetesa pomoću antagonista faktora inhibicije migracije makrofaga (S,R)-3-(4-hidroksifenil)-4,5-dihidro-5-izoksazol metil estra sirćetne kiseline
Control of the of the final stage of immune-mediated diabetes by ISO-1, an antagonist of macrophage migration inhibitory factor
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We recently showed that attenuation of inflammatory cytokine MIF with pharmacological inhibitor ISO-1 down-regulates the immune-mediated diabetes in mice. Here we explore the effects of MIF neutralization by ISO-1 on the local inflammatory pathway of the disease. In vivo treatment of mice with ISO-1 inhibited the expression of pro-inflammatory cytokines and iNOS in the pancreatic islets. Moreover, ISO-1 affected in vitro cytokine-induced NO production by fibroblasts, endothelial cells, insulinoma cells, and pancreatic islets, and rescued β cells from NO-dependent damage. These results suggest regulatory potential of ISO-1 at the level of the pancreas which can preserve the target tissue from autoimmune attack.
Keywords:Macrophage migration inhibitory factor (MIF); autoimmunity; diabetes; (S,R)-3-(4-hydroxyphenil)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1); nitric oxide (NO); IL-18 - IL-1β
Source:Archives of Biological Sciences, 2008, 60, 3, 389-401