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- Title
Improved intraportal islet transplantation outcome by systemic IKK-beta inhibition: NF-κB activity in pancreatic islets depends on oxygen availability.
- Authors
Chen, C; Moreno, R; Samikannu, B; Bretzel, R G; Schmitz, M L; Linn, T
- Abstract
Intraportal islet transplantation suffers from low efficiency caused by substantial islet mass loss after transplantation. How this process is regulated is still unclear. Here, we show that NF-κB activation was detectable in islet grafts shortly after transplantation of porcine islets to diabetic NMRI nu/nu mice, and systemic NF-κB inhibition in transplanted animals significantly prolonged islet graft survival. Proinflammatory cytokines alone did not cause evident cell death in pancreatic islet within 24 h, while the combination of cytokines with hypoxia resulted in a strong induction of cell death that could be blocked dose-dependently by a selective IKK-β inhibitor. Under hypoxia, NF-κB activity impaired expression of antiapoptotic gene BCL-xL, c-FLIP and survivin. NF-κB activation in isolated islets was reduced by hypoxia in a time-dependent manner, accordingly, NF-κB activation in transplanted islets diminished by time. Our data indicate that, while NF-κB has an antiapoptotic role under normoxia, low oxygen conditions decrease its activity and transform it to a proapoptotic transcription factor in pancreatic islets. We conclude that NF-κB inhibition represents a potential strategy to improve islet transplantation efficiency.
- Publication
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2011, Vol 11, Issue 2, p215
- ISSN
1600-6143
- Publication type
Journal Article
- DOI
10.1111/j.1600-6143.2010.03390.x