PT  - JOURNAL ARTICLE
AU  - Giannoukakis, N
AU  - Rudert, W A
AU  - Ghivizzani, S C
AU  - Gambotto, A
AU  - Ricordi, C
AU  - Trucco, M
AU  - Robbins, P D
TI  - Adenoviral gene transfer of the interleukin-1 receptor antagonist protein to human islets prevents IL-1beta-induced beta-cell impairment and activation of islet cell apoptosis in vitro.
AID  - 10.2337/diabetes.48.9.1730
DP  - 1999 Sep 01
TA  - Diabetes
PG  - 1730--1736
VI  - 48
IP  - 9
4099  - http://diabetes.diabetesjournals.org/content/48/9/1730.short
4100  - http://diabetes.diabetesjournals.org/content/48/9/1730.full
SO  - Diabetes1999 Sep 01; 48
AB  - The beta-cells in the pancreatic islets of Langerhans are the targets of autoreactive T-cells and are destroyed in type 1 diabetes. Macrophage-derived interleukin-1beta (IL-1beta) is important in eliciting beta-cell dysfunction and initiating beta-cell damage in response to microenvironmental changes within islets. In particular, IL-1beta can impair glucose-stimulated insulin production in beta-cells in vitro and can sensitize them to Fas (CD95)/FasL-triggered apoptosis. In this report, we have examined the ability to block the detrimental effects of IL-1beta by genetically modifying islets by adenoviral gene transfer to express the IL-1 receptor antagonist protein. We demonstrate that adenoviral gene delivery of the cDNA encoding the interleukin-1 receptor antagonist protein (IL-1Ra) to cultured islets results in protection of human islets in vitro against IL-1beta-induced nitric oxide formation, impairment in glucose-stimulated insulin production, and Fas-triggered apoptosis activation. Our results further support the hypothesis that IL-1beta antagonism in in situ may prevent intra-islet proinsulitic inflammatory events and may allow for an in vivo gene therapy strategy to prevent insulitis and the consequent pathogenesis of diabetes.