IL-23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocin
IL-23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocin
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DOI：
10.1002/eji.200535325
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发表时间：
2006-01-01
影响因子：
5.4
通讯作者：
Lukic, ML
中科院分区：
文献类型：
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作者：
Mensah-Brown, EPK;Shahin, A;Lukic, ML
IL-23是IL-17的近端调节因子，可能是诱导自身免疫性炎症的主要驱动力。我们在雄性C57BL/6小鼠中采用低剂量链脲唑菌素（MLD-STZ； 4 × 40 mg/kg体重）治疗亚糖尿病模型，通过血糖、定量组织学、免疫组织化学和胰岛相关细胞因子的表达来评估IL-23对免疫介导的β细胞损伤和糖尿病发展的影响。从MLD-STZ给药的第一天开始，每天10次注射400 ng IL-23，与对照组（无IL-23）相比，导致显著且持续的高血糖和体重减轻，浸润细胞数量显著增加，胰岛素含量降低，凋亡增强，ifn - γ和IL-17的表达（对照组未见），胰岛中tnf - α和IL-18的表达显著增加。在MLD-STZ给药前5天开始IL-23治疗对胰岛的糖尿病发生或细胞因子表达没有影响。我们在动物模型中提供了IL-23通过诱导靶组织中IL-17和可能的ifn - γ产生参与1型糖尿病发展的第一个证据。
IL-23, a proximal regulator of IL-17, may be a major driving force in the induction of autoimmune inflammation. We have used a model of subdiabetogenic treatment with multiple low doses of streptozotocin (MLD-STZ; 4 x 40 mg/kg body weight) in male C57BL/6 mice to study the effect of IL-23 on immune-mediated beta cell damage and the development of diabetes, as evaluated by blood glucose, quantitative histology, immunohistochemistry and expression of relevant cytokines in the islets. Ten daily injections of 400 ng IL-23, starting on the first day of MLD-STZ administration led to significant and sustained hyperglycemia along with weight loss compared with controls (no IL-23), and a significant increase in the number of infiltrating cells, a lower insulin content, enhanced apoptosis, expression of IFN-gamma and IL-17 (not seen in the controls) and a significant increase in the expression of TNF-alpha and IL-18 in the pancreatic islets. IL-23 treatment started 5 days prior to MLD-STZ administration had no effect on diabetogenesis or cytokines expression in the pancreatic islets. We provide the first evidence in an animal model that IL-23 is involved in the development of type-1 diabetes, by inducing IL-17 and possibly IFN-gamma production in the target tissue.