Adenoviral Gene Transfer of the Interleukin-1 Receptor Antagonist Protein to Human Islets Prevents IL-1β-Induced β-Cell Impairment and Activation of Islet Cell Apoptosis In Vitro

摘要

The β-cells in the pancreatic islets of Langerhans are the targets of autoreactive T-cells and are destroyed in type 1 diabetes. Macrophage-derived interleukin-1β (IL-1β) is important in eliciting β-cell dysfunction and initiating β-cell damage in response to microenviron- mental changes within islets. In particular, IL-1β can impair glucose-stimulated insulin production in β-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-1β by genetically modifying islets by adenoviral gene transfer to express the IL-1 receptor antagonist protein.