Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Transplant. 2011 Feb;11(2):215-24. doi: 10.1111/j.1600-6143.2010.03390.x. Epub 2011 Jan 10.

Improved intraportal islet transplantation outcome by systemic IKK-beta inhibition: NF-κB activity in pancreatic islets depends on oxygen availability.

Author information

  • 1Third Medical Department Institute of Biochemistry, Medical Faculty, Justus-Liebig University Giessen, Giessen, Germany.

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.

©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

PMID:
21219576
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Blackwell Publishing
    Loading ...
    Write to the Help Desk