Protection of human islets from the effects of interleukin-1β by adenoviral gene transfer of an IκB repressor

Nick Giannoukakis, William A. Rudert, Massimo Trucco, Paul D. Robbins

Research output: Contribution to journalArticle

188 Scopus citations

Abstract

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that inhibits β cell function and promotes Fas-triggered apoptosis. IL-1β is thought to act early in the initiation of the autoimmune destruction of pancreatic β cells in type I diabetes. IL-1β promotes β cell impairment, in part, by activating NF-κB transcription factor-dependent signaling pathways. We have examined whether cells could be protected from the effects of IL-1β by overexpressing an inhibitor of NF-κB activity, IκB, by adenoviral gene transfer to intact human islets in culture. Infection of islets with an adenoviral vector encoding a non-phosphorylatable, non-degradable variant of IκBα resulted in normal insulin responses to glucose in the presence of IL-1β. Furthermore, nitric oxide production was prevented and, more importantly, Fas-triggered apoptosis was inhibited following IκBα gene transfer. These results suggest that blocking the NF-κB pathway might prevent cytokine-induced β cell impairment as a means of facilitating islet transplantation.

Original languageEnglish (US)
Pages (from-to)36509-36513
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number47
DOIs
StatePublished - Nov 24 2000
Externally publishedYes

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