Caspase-1 is not required for type 1 diabetes in the NOD mouse.
Document Type
Article
Publication Date
2004
Keywords
Comparative-Study, Diabetes-Mellitus-Experimental, Diabetes-Mellitus-Type-I, Female, Incidence, Interleukin-1, Interleukin-18, Kinetics, Lipopolysaccharides, Macrophages, Male, Mice, Mice-Inbred-NOD, Mice-Knockout, Sex-Characteristics, Species-Specificity, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Tumor-Necrosis-Factor
First Page
99
Last Page
104
JAX Source
Diabetes 2004 Jan; 53(1):99-104.
Abstract
Interleukin (IL)-1 beta and IL-18 are two cytokines associated with the immunopathogenesis of diabetes in NOD mice. Both of these cytokines are cleaved by caspase-1 to their biologically active forms. IL-1 is a proinflammatory cytokine linked to beta-cell damage, and IL-18 stimulates production of interferon (IFN)gamma in synergy with IL-12. To examine the effects produced by caspase-1 deficiency on diabetes development in NOD/Lt mice, a disrupted Casp1 gene was introduced by a speed congenic technique. Casp1(-/-) bone marrow-derived macrophages stimulated with lipopolysaccharide produced no detectable IL-18, fourfold lower IL-1 beta, and 20-30% less IL-1 alpha than macrophages from wild-type Casp1(+/+) or Casp1(+/-) controls. Unexpectedly, despite reduced IL-1 and IL-18, there was no change in the rate of diabetes or in total incidence as compared with that in wild-type NOD mice. IL-1 reportedly makes an important pathological contribution in the multidose streptozotocin model of diabetes; however, there was no difference in sensitivity to streptozotocin between NOD mice and NOD.Casp1(-/-) mice at 40 mg/kg body wt or at 25 mg/kg body wt dosage levels. These findings show that caspase-1 processing of IL-1 beta and IL-18 is not absolutely required for mediation of spontaneous or chemically induced diabetes pathogenesis in the NOD mouse.
Recommended Citation
Schott WH,
Haskell BD,
Tse HM,
Milton MJ,
Piganelli JD,
Choisy RC,
Reifsnyder PC,
Chervonsky AV,
Leiter EH.
Caspase-1 is not required for type 1 diabetes in the NOD mouse. Diabetes 2004 Jan; 53(1):99-104.