Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, 250012, China.
Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, 250012, China.
Biomed Pharmacother. 2017 Oct;94:619-626. doi: 10.1016/j.biopha.2017.07.102. Epub 2017 Aug 4.
NLRP3 and NLRP1 inflammasomes signaling pathways may play an important role in the development and progression of type 1 diabetes mellitus (T1DM). However, relative research is rare.
The blood mononuclear cells (PBMCs) and granulocytes (GCs) were collected from T1DM patients. The mRNA and protein expression levels were detected by qRT-PCR and Western blotting, respectively. The NLRP3/NLRP1was knocked down by transfected with siRNA, or ovexpressed by infected with lentiviral vectors in PBMCs and GCs from non obese diabetic (NOD) mice, respectively. The occurrence of diabetes was evaluated and the intraperitoneal glucose tolerance was tested in NOD mice with IL-1 receptor-associated kinase-M deficiency (IRAK-M). The pancreas and lymphonodus of IRAK-M NOD mice were also collected for detection of NLRP3/NLRP1 expression.
NLRP3, NLRP1, Caspase-1and IL-1β were significantly downregulated in the PBMCs and GCs of patients with T1DM, and NLRP3 and NLRP1 were markedly downregulated in T1DM patients with DKA compared to that with ND and CC. Further study indicated that IL-1β mRNA expression level was positively correlated with the expression levels of NLRP3, NLRP1 and Caspase-1. Besides, NLRP3/NLRP1 knockdown decreased the expression levels of Caspase-1 and IL-1β; whereas NLRP3/NLRP1 overexpression increased the expression levels of Caspase-1 and IL-1β in vitro. IRAK-M NOD mice had early onset and rapid progression of T1DM, and weak glucose tolerance, which was regarded as an early T1D mouse model. The mRNA expression levels of NLRP3, NLRP1, Caspase-1and IL-1β in the pancreas and lymphonodus of IRAK-M NOD mice were significantly higher compared to that of IRAK-M NOD mice.
NLRP3 and NLRP1 inflammasomes signaling pathways were associated with the development and progression of T1DM, which response as protective factors in the early stage of T1DM.
NLRP3 和 NLRP1 炎性小体信号通路可能在 1 型糖尿病（T1DM）的发生和发展中起重要作用。然而，相关研究较少。
收集 T1DM 患者的外周血单个核细胞（PBMCs）和粒细胞（GCs）。通过 qRT-PCR 和 Western blot 分别检测其 mRNA 和蛋白表达水平。通过转染 siRNA 或感染慢病毒载体，分别在非肥胖型糖尿病（NOD）小鼠的 PBMCs 和 GCs 中敲低 NLRP3/NLRP1 的表达，或过表达 NLRP3/NLRP1。在白细胞介素-1 受体相关激酶-M 缺陷（IRAK-M）的 NOD 小鼠中评估糖尿病的发生，并进行腹腔内葡萄糖耐量试验。收集 IRAK-M NOD 小鼠的胰腺和淋巴结，检测 NLRP3/NLRP1 的表达。
T1DM 患者 PBMCs 和 GCs 中 NLRP3、NLRP1、Caspase-1 和 IL-1β 的表达明显下调，与 ND 和 CC 相比，DKA 患者 T1DM 患者中 NLRP3 和 NLRP1 的表达明显下调。进一步研究表明，IL-1βmRNA 表达水平与 NLRP3、NLRP1 和 Caspase-1 的表达水平呈正相关。此外，体外 NLRP3/NLRP1 敲低降低了 Caspase-1 和 IL-1β 的表达水平；而 NLRP3/NLRP1 过表达则增加了 Caspase-1 和 IL-1β 的表达水平。IRAK-M NOD 小鼠的 T1DM 发病早，进展快，葡萄糖耐量差，被认为是一种早期 T1D 小鼠模型。IRAK-M NOD 小鼠胰腺和淋巴结中 NLRP3、NLRP1、Caspase-1 和 IL-1β 的 mRNA 表达水平明显高于 IRAK-M NOD 小鼠。
NLRP3 和 NLRP1 炎性小体信号通路与 T1DM 的发生和发展有关，在 T1DM 的早期阶段作为保护因素发挥作用。
