IL-1 receptor deficiency slows progression to diabetes in the NOD mouse
- Author(s)
- Thomas, HE; Irawaty, W; Darwiche, R; Brodnicki, TC; Santamaria, P; Allison, J; Kay, TWH;
- Details
- Publication Year 2004-01-01,Volume 53,Issue #1,Page 113-121
- Journal Title
- DIABETES
- Publication Type
- Journal Article
- Abstract
- Proinflammatory cytokines are believed to be important in pancreatic beta-cell destruction in the development of type 1 diabetes. They act by upregulation of genes including Fas and inducible nitric oxide synthase (iNOS), which have both been shown to lead to beta-cell death in vitro. We used mice deficient in the interleukin (IL)-1 receptor (IL-1R) to assess the contribution of IL-1 to different models of diabetes. IL-1R-deficient islets were protected from the damaging effects of tumor necrosis factor (TNF) and interferon (IFN)-gamma in vitro, and beta-cell expression of iNOS was reduced, suggesting that IL-1 mediates the induction of iNOS by TNF and IFN-gamma. IL-1 action was not required for induction of class I major histocompatibility complex or Fas by TNF and IFN-gamma. IL-1R-deficient nonobese diabetic (NOD) mice developed diabetes significantly slower than wildtype mice. IL-1R deficiency did not affect diabetes in 8.3 TCR transgenic NOD mice but prolonged the time to diabetes in BDC2.5 TCR transgenic NOD mice. We conclude that IL-1R deficiency slows progression to diabetes in NOD mice but on its own does not prevent diabetes.
- Publisher
- AMER DIABETES ASSOC
- Keywords
- NITRIC-OXIDE SYNTHASE; BETA-CELL DESTRUCTION; NECROSIS-FACTOR-ALPHA; PANCREATIC-ISLETS; T-CELL; INTERLEUKIN-1 RECEPTOR; INSULIN-SECRETION; FLOW-CYTOMETRY; I RECEPTOR; MICE
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Creation Date: 2004-01-01 12:00:00