Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes.
The activation of the transcription factor NF-κB leads to changes in expression of many genes in pancreatic β-cells. However, the role of NF-κB activation in islet transplantation has not been fully elucidated. The aim of the present study was to investigate whether the state of NF-κB activation wou...
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2013
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oai:doaj.org-article:342a868255eb493da4e9de391aaf79a32021-11-18T08:50:21ZSustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes.1932-620310.1371/journal.pone.0077452https://doaj.org/article/342a868255eb493da4e9de391aaf79a32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24204831/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The activation of the transcription factor NF-κB leads to changes in expression of many genes in pancreatic β-cells. However, the role of NF-κB activation in islet transplantation has not been fully elucidated. The aim of the present study was to investigate whether the state of NF-κB activation would influence the outcome of islet transplantation. Transgenic mice expressing a dominant active IKKβ (constitutively active) or a non-degradable form of IκBα (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-κB) 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 IκBα when compared to wild type controls. However, the transplantation outcomes using islets isolated from mice expressing a constitutively active mutant of NF-κB 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-κB 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.Aileen J F KingYongjing GuoDongsheng CaiJennifer Hollister-LockBrooke MorrisAlison SalvatoriJohn A CorbettSusan Bonner-WeirSteven E ShoelsonGordon C WeirPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e77452 (2013) |
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Medicine R Science Q |
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Medicine R Science Q Aileen J F King Yongjing Guo Dongsheng Cai Jennifer Hollister-Lock Brooke Morris Alison Salvatori John A Corbett Susan Bonner-Weir Steven E Shoelson Gordon C Weir Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes. |
| description |
The activation of the transcription factor NF-κB leads to changes in expression of many genes in pancreatic β-cells. However, the role of NF-κB activation in islet transplantation has not been fully elucidated. The aim of the present study was to investigate whether the state of NF-κB activation would influence the outcome of islet transplantation. Transgenic mice expressing a dominant active IKKβ (constitutively active) or a non-degradable form of IκBα (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-κB) 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 IκBα when compared to wild type controls. However, the transplantation outcomes using islets isolated from mice expressing a constitutively active mutant of NF-κB 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-κB 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. |
| format |
article |
| author |
Aileen J F King Yongjing Guo Dongsheng Cai Jennifer Hollister-Lock Brooke Morris Alison Salvatori John A Corbett Susan Bonner-Weir Steven E Shoelson Gordon C Weir |
| author_facet |
Aileen J F King Yongjing Guo Dongsheng Cai Jennifer Hollister-Lock Brooke Morris Alison Salvatori John A Corbett Susan Bonner-Weir Steven E Shoelson Gordon C Weir |
| author_sort |
Aileen J F King |
| title |
Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes. |
| title_short |
Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes. |
| title_full |
Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes. |
| title_fullStr |
Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes. |
| title_full_unstemmed |
Sustained NF-κB activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes. |
| title_sort |
sustained nf-κb activation and inhibition in β-cells have minimal effects on function and islet transplant outcomes. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/342a868255eb493da4e9de391aaf79a3 |
| work_keys_str_mv |
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