| First Author | Kim S | Year | 2007 |
| Journal | Proc Natl Acad Sci U S A | Volume | 104 |
| Issue | 6 | Pages | 1913-8 |
| PubMed ID | 17267600 | Mgi Jnum | J:119747 |
| Mgi Id | MGI:3703213 | Doi | 10.1073/pnas.0610690104 |
| Citation | Kim S, et al. (2007) NF-kappa B prevents beta cell death and autoimmune diabetes in NOD mice. Proc Natl Acad Sci U S A 104(6):1913-8 |
| abstractText | Whereas NF-kappaB has potent antiapoptotic function in most cell types, it was reported that in pancreatic beta cells it serves a proapoptotic function and may contribute to the pathogenesis of autoimmune type 1 diabetes. To investigate the role of beta cell NF-kappaB in autoimmune diabetes, we produced transgenic mice expressing a nondegradable form of IkappaBalpha in pancreatic beta cells (RIP-mIkappaBalpha mice). beta cells of these mice were more susceptible to killing by TNF-alpha plus IFN-gamma but more resistant to IL-1beta plus IFN-gamma than normal beta cells. Similar results were obtained with beta cells lacking IkappaB kinase beta, a protein kinase required for NF-kappaB activation. Inhibition of beta cell NF-kappaB accelerated the development of autoimmune diabetes in nonobese diabetic mice but had no effect on glucose tolerance or serum insulin in C57BL/6 mice, precluding a nonphysiological effect of transgene expression. Development of diabetes after transfer of diabetogenic CD4(+) T cells was accelerated in RIP-mIkappaBalpha/nonobese diabetic mice and was abrogated by anti-TNF therapy. These results suggest that under conditions that resemble autoimmune type 1 diabetes, the dominant effect of NF-kappaB is prevention of TNF-induced apoptosis. This differs from the proapoptotic function of NF-kappaB in IL-1beta-stimulated beta cells. |
