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

Abstract

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.Nedavno smo pokazali da neutralizacija inflamatornog citokina MIF-a farmakološkim inhibitorom ISO-1 negativno reguliše imunski posredovan dijabetes miševa. U ovom radu ispitivali smo efekte neutralizacije MIF-a pomoću ISO-1 na lokalne inflamatorne puteve bolesti. In vivo tretman miševa pomoću ISO-1 je inhibirao ekspresiju proinflamatornih citokina i inducibilne sintaze azot monoksida u ostrvcima pankreasa. Štaviše, ISO-1 je remetio in vitro produkciju azot monoksida indukovan u citokinima u fibroblastima, ćelijama endotela, insulinomama i pankreasnih ostrvaca i tako sačuvao beta ćelije od oštećenja izazvanih azot monoksidom. Ovi rezultati ukazuju na regulatorni potencijal ISO-1 na nivou ciljnog tkiva koji štiti ciljno tkivo od autoimunog ataka.Projekat ministarstva br. 143029