Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome.
Insulin Reduces Inflammation by Regulating the Activation of the NLRP3 Inflammasome.
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DOI：
10.3389/fimmu.2020.587229
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发表时间：
2020
影响因子：
7.3
通讯作者：
Chen YH
中科院分区：
文献类型：
--
作者：
Chang YW;Hung LC;Chen YC;Wang WH;Lin CY;Tzeng HH;Suen JL;Chen YH
含有NOD、LRR和pyrin结构域的蛋白3（NLRP 3）炎性体是IL-1β成熟的平台，旨在介导针对必须严格调节的危险信号的快速免疫应答。众所周知，胰岛素是维持葡萄糖生理反应的关键激素。胰岛素具有抗炎作用，但其免疫调节的分子机制尚不清楚。在这里，我们研究了胰岛素是否通过调节NLRP 3炎性体来减少炎症。在本研究中，我们使用LPS和ATP诱导细胞内NLRP 3炎性体的形成。胰岛素通过阻止THP-1细胞和人CD 14+单核细胞源性巨噬细胞中ASC的组装来抑制IL-1β的分泌。胰岛素改变了Syk、p38丝裂原活化蛋白激酶（MAPK）和ASC的磷酸化状态。这些作用在用靶向胰岛素受体的小干扰RNA转染的THP-1细胞中减弱。在体内，葡萄糖-胰岛素-钾可降低LPS致小鼠血清IL-1β水平，减少肠壁ASC斑形成，减少局部巨噬细胞浸润，减轻肠壁损伤。胰岛素可能通过调节NLRP 3炎性体发挥免疫调节作用。
The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is the platform for IL-1β maturation, aimed at mediating a rapid immune response against danger signals which must be tightly regulated. Insulin is well known as the critical hormone in the maintenance of glucose in physiologic response. Previous studies have proved insulin has the anti-inflammatory effect but the molecular mechanism of immunomodulation provided by insulin is not clear so far. Here we investigated whether insulin reduces inflammation by regulating the NLRP3 inflammasome. In the present study, we used LPS and ATP to induce the intracellular formation of the NLRP3 inflammasome. Insulin inhibited the secretion of IL-1β by preventing the assembly of the ASC in THP-1 cells and human CD14+ monocyte-derived macrophages. The phosphorylation status of Syk, p38 mitogen−activated protein kinase (MAPK) and ASC were altered by insulin. These effects were attenuated in THP-1 cells transfected with small interfering RNA targeting insulin receptors. In vivo, administration of glucose–insulin–potassium reduced serum IL-1β level, intestinal ASC speck formation, local macrophage infiltration and alleviated intestinal injury in mice exposed to LPS. Insulin may play an immunomodulatory role in anti-inflammation by regulating the NLRP3 inflammasome.