NF-κB is weakly activated in the NOD mouse model of type 1 diabetes.
NF-κB is weakly activated in the NOD mouse model of type 1 diabetes.
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DOI：
10.1038/s41598-018-22738-3
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发表时间：
2018-03-09
影响因子：
4.6
通讯作者：
Kay TWH
中科院分区：
文献类型：
--
作者：
Irvin AE;Jhala G;Zhao Y;Blackwell TS;Krishnamurthy B;Thomas HE;Kay TWH
1型糖尿病是一种自身免疫性疾病，其特征是免疫系统选择性地破坏胰岛β细胞。转录因子核因子-kappaB(NF-κB)调节先天免疫和获得性免疫反应。利用基因打靶和胰岛和免疫细胞的体外分析，NF-κB的激活与1型糖尿病的发展有关。在这里，我们使用非肥胖糖尿病(NOD)小鼠模型，该模型表达转录活性的NF-κB的荧光素酶报告，以确定其在糖尿病发展过程中的体内激活。在体外和体内用Toll样受体配体处理后，很容易检测到荧光素酶活性增加，这表明NF-κB被激活。然而，在未处理的NOD小鼠中，激活的NF-κB在低水平的本底水平上被检测到，但不随年龄变化，尽管随着时间的推移胰岛炎症渗透的进展。在需要κ+T细胞和炎性巨噬细胞的1型糖尿病加速模型中，核因子-CD4B被高度激活。这些数据揭示了1型糖尿病发展过程中炎症反应的本质。
Type 1 diabetes is an autoimmune disease characterised by selective destruction of pancreatic beta cells by the immune system. The transcription factor nuclear factor-kappa B (NF-κB) regulates innate and adaptive immune responses. Using gene targeting and in vitro analysis of pancreatic islets and immune cells, NF-κB activation has been implicated in type 1 diabetes development. Here we use a non-obese diabetic (NOD) mouse model that expresses a luciferase reporter of transcriptionally active NF-κB to determine its activation in vivo during development of diabetes. Increased luciferase activity was readily detected upon treatment with Toll-like receptor ligands in vitro and in vivo, indicating activation of NF-κB. However, activated NF-κB was detectable at low levels above background in unmanipulated NOD mice, but did not vary with age, despite the progression of inflammatory infiltration in islets over time. NF-κB was highly activated in an accelerated model of type 1 diabetes that requires CD4+ T cells and inflammatory macrophages. These data shed light on the nature of the inflammatory response in the development of type 1 diabetes.
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影响因子：
3.7
作者：
Carrero JA;Calderon B;Towfic F;Artyomov MN;Unanue ER
通讯作者：
Unanue ER
通过强烈的激动剂胰岛素模拟蛋白的耐受性疫苗接种，预防小鼠中1型糖尿病。
DOI：
10.1084/jem.20110574
发表时间：
2011-07-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Daniel C;Weigmann B;Bronson R;von Boehmer H
通讯作者：
von Boehmer H
影响因子：
7.7
作者：
Matos, M;Park, R;Benoist, C
通讯作者：
Benoist, C
影响因子：
4.4
作者：
Weaver, DJ;Poligone, B;Tisch, R
通讯作者：
Tisch, R
影响因子：
4.4
作者：
Kanagawa, O;Militech, A;Vaupel, BA
通讯作者：
Vaupel, BA