| First Author | Schott WH | Year | 2004 |
| Journal | Diabetes | Volume | 53 |
| Issue | 1 | Pages | 99-104 |
| PubMed ID | 14693703 | Mgi Jnum | J:87250 |
| Mgi Id | MGI:2683970 | Doi | 10.2337/diabetes.53.1.99 |
| Citation | Schott WH, et al. (2004) Caspase-1 Is Not Required for Type 1 Diabetes in the NOD Mouse. Diabetes 53(1):99-104 |
| abstractText | Interleukin (IL)-1beta 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-1beta, and 20-30% less IL-1alpha 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-1beta and IL-18 is not absolutely required for mediation of spontaneous or chemically induced diabetes pathogenesis in the NOD mouse. |
