Adenoviral gene transfer of the interleukin-1 receptor antagonist protein to human islets prevents IL-lβ-induced β-cell impairment and activation of islet cell apoptosis in vitro

Nick Giannoukakis, William A. Rudert, Steve C. Ghivizzani, Andrea Gambotto, Camillo Ricordi, Massimo Trucco, Paul D. Robbins

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

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-lβ (IL-1β) is important in eliciting β-cell dysfunction and initiating β-cell damage in response to microenvironmental 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. 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-lβ-induced nitric oxide formation, impairment in glucose-stimulated insulin production, and Fas- triggered apoptosis activation. Our results further support the hypothesis that IL-1β 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.

Original languageEnglish
Pages (from-to)1730-1736
Number of pages7
JournalDiabetes
Volume48
Issue number9
DOIs
StatePublished - Sep 11 1999

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Interleukin-1
Islets of Langerhans
Apoptosis
Genes
Insulin
Interleukin 1 Receptor Antagonist Protein
Glucose
Interleukin-1 Receptors
Interleukins
Type 1 Diabetes Mellitus
Genetic Therapy
Nitric Oxide
Complementary DNA
Macrophages
T-Lymphocytes
human IL1RN protein
In Vitro Techniques
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Adenoviral gene transfer of the interleukin-1 receptor antagonist protein to human islets prevents IL-lβ-induced β-cell impairment and activation of islet cell apoptosis in vitro. / Giannoukakis, Nick; Rudert, William A.; Ghivizzani, Steve C.; Gambotto, Andrea; Ricordi, Camillo; Trucco, Massimo; Robbins, Paul D.

In: Diabetes, Vol. 48, No. 9, 11.09.1999, p. 1730-1736.

Research output: Contribution to journalArticle

Giannoukakis, Nick ; Rudert, William A. ; Ghivizzani, Steve C. ; Gambotto, Andrea ; Ricordi, Camillo ; Trucco, Massimo ; Robbins, Paul D. / Adenoviral gene transfer of the interleukin-1 receptor antagonist protein to human islets prevents IL-lβ-induced β-cell impairment and activation of islet cell apoptosis in vitro. In: Diabetes. 1999 ; Vol. 48, No. 9. pp. 1730-1736.
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