| First Author | Stojanovic I | Year | 2012 |
| Journal | Clin Exp Immunol | Volume | 169 |
| Issue | 2 | Pages | 156-63 |
| PubMed ID | 22774990 | Mgi Jnum | J:188289 |
| Mgi Id | MGI:5440131 | Doi | 10.1111/j.1365-2249.2012.04607.x |
| Citation | Stojanovic I, et al. (2012) Macrophage migration inhibitory factor deficiency protects pancreatic islets from cytokine-induced apoptosis in vitro. Clin Exp Immunol 169(2):156-63 |
| abstractText | During pathogenesis of diabetes, pancreatic islets are exposed to high levels of cytokines and other inflammatory mediators that induce deterioration of insulin-producing beta cells. Macrophage migration inhibitory factor (MIF) plays a key role in the onset and development of several immunoinflammatory diseases and also controls apoptotic cell death. Because the occurrence of apoptosis plays a pathogenetic role in beta cell death during type 1 diabetes development and MIF is expressed in beta cells, we explored the influence of MIF deficiency on cytokine-induced apoptosis in pancreatic islets. The results indicated clearly that elevated MIF secretion preceded C57BL/6 pancreatic islets death induced by interferon (IFN)-gamma + tumour necrosis factor (TNF)-alpha + interleukin (IL)-1beta. Consequently, MIF-deficient [MIF-knock-out (KO)] pancreatic islets or islet cells showed significant resistance to cytokine-induced death than those isolated from C57BL/6 mice. Furthermore, upon exposure to cytokines pancreatic islets from MIF-KO mice maintained normal insulin expression and produced less cyclooxygenase-2 (COX-2) than those from wild-type C57BL6 mice. The final outcome of cytokine-induced islet apoptosis in islets from wild-type mice was the activation of mitochondrial membrane pore-forming protein Bcl-2-associated X protein and effector caspase 3. In contrast, these apoptotic mediators remained at normal levels in islets from MIF-KO mice suggesting that MIF absence prevented initiation of the mitochondrial apoptotic pathway. Additionally, the protection from apoptosis was also mediated by up-regulation of prosurvival kinase extracellular-regulated kinase 1/2 in MIF-KO islets. These data indicate that MIF is involved in the propagation of pancreatic islets apoptosis probably via nuclear factor-kappaB and mitochondria-related proteins. |
