Control of the of the final stage of immune-mediated diabetes by ISO-1, an antagonist of macrophage migration inhibitory factor

• Main Authors: Stojanović Ivana, Maksimović-Ivanić Danijela, Al-Abed Y., Nicoletti F., Stošić-Grujičić Stanislava
• Format: Article
• Language: English
• Published: University of Belgrade, University of Novi Sad 2008-01-01
• Series: Archives of Biological Sciences
• Subjects: 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
• Online Access: http://www.doiserbia.nb.rs/img/doi/0354-4664/2008/0354-46640803389S.pdf

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.