First Author | King AJ | Year | 2013 |
Journal | PLoS One | Volume | 8 |
Issue | 10 | Pages | e77452 |
PubMed ID | 24204831 | Mgi Jnum | J:209174 |
Mgi Id | MGI:5566583 | Doi | 10.1371/journal.pone.0077452 |
Citation | King AJ, et al. (2013) Sustained NF-kappaB activation and inhibition in beta-cells have minimal effects on function and islet transplant outcomes. PLoS One 8(10):e77452 |
abstractText | The activation of the transcription factor NF-kappaB leads to changes in expression of many genes in pancreatic beta-cells. However, the role of NF-kappaB activation in islet transplantation has not been fully elucidated. The aim of the present study was to investigate whether the state of NF-kappaB activation would influence the outcome of islet transplantation. Transgenic mice expressing a dominant active IKKbeta (constitutively active) or a non-degradable form of IkappaBalpha (constitutive inhibition) under control of the rat insulin promoter were generated. Islets from these mice were transplanted into streptozotocin diabetic mice in suboptimal numbers. Further, the effects of salicylate (an inhibitor of NF-kappaB) treatment of normal islets prior to transplantation, and the effects of salicylate administration to mice prior to and after islet implantation were evaluated. Transplantation outcomes were not affected using islets expressing a non-degradable form of IkappaBalpha when compared to wild type controls. However, the transplantation outcomes using islets isolated from mice expressing a constitutively active mutant of NF-kappaB were marginally worse, although no aberrations of islet function in vitro could be detected. Salicylate treatment of normal islets or mice had no effect on transplantation outcome. The current study draws attention to the complexities of NF-kappaB in pancreatic beta cells by suggesting that they can adapt with normal or near normal function to both chronic activation and inhibition of this important transcription factor. |