TRPM2 ion channels regulate macrophage polarization and gastric inflammation during Helicobacter pylori infection.
TRPM2 ion channels regulate macrophage polarization and gastric inflammation during Helicobacter pylori infection.
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TRPM2离子通道调节幽门螺杆菌感染期间巨噬细胞极化和胃炎。
DOI：
10.1038/mi.2016.60
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发表时间：
2017-03
影响因子：
8
通讯作者：
Partida-Sánchez S
中科院分区：
文献类型：
--
作者：
Beceiro S;Radin JN;Chatuvedi R;Piazuelo MB;Horvarth DJ;Cortado H;Gu Y;Dixon B;Gu C;Lange I;Koomoa DL;Wilson KT;Algood HM;Partida-Sánchez S
吞噬细胞中的钙信号传导对于细胞活化、迁移和感染或炎症的潜在解决是必需的。通过激活巨噬细胞中NADPH（烟酰胺腺嘌呤二核苷酸磷酸）氧化酶活性产生活性氧（ROS）与细胞内钙浓度的改变有关。由于其在吞噬细胞中作为氧化应激传感器的作用，我们研究了阳离子通道瞬时受体电位melastatin 2（TRPM 2）在幽门螺杆菌感染诱导的氧化应激反应中在巨噬细胞中的功能。我们发现，Trpm 2 −/−小鼠，当慢性感染H。pylori感染的小鼠表现出增加的胃炎症和减少的细菌定植。TRPM2的缺乏触发了更大的巨噬细胞产生炎症介质，并促进经典激活的巨噬细胞M1极化响应H。幽门。TRPM2缺陷型巨噬细胞对H.幽门螺杆菌刺激不能控制细胞内钙水平，导致钙超载。此外，与WT巨噬细胞相比，TRPM 2 −/−巨噬细胞中细胞内钙的增加增强了MAPK和NADPH氧化酶的活性。我们的数据表明，TRPM2缺失增加的ROS和炎性细胞因子的产生调节了巨噬细胞的氧化应激，从而降低了H。幽门螺杆菌胃定植，同时增加胃粘膜炎症。
Calcium signaling in phagocytes is essential for cellular activation, migration and the potential resolution of infection or inflammation. The generation of reactive oxygen species (ROS) via activation of NADPH (nicotinamide adenine dinucleotide phosphate-) oxidase activity in macrophages has been linked to altered intracellular calcium concentrations. Because of its role as an oxidative stress sensor in phagocytes, we investigated the function of the cation channel transient receptor potential melastatin 2 (TRPM2) in macrophages during oxidative stress responses induced by Helicobacter pylori infection. We show that Trpm2−/− mice, when chronically infected with H. pylori, exhibit increased gastric inflammation and decreased bacterial colonization compared with WT mice. The absence of TRPM2 triggers greater macrophage production of inflammatory mediators and promotes classically activated macrophage M1 polarization in response to H. pylori. TRPM2-deficient macrophages upon H. pylori stimulation are unable to control intracellular calcium levels, which results in calcium overloading. Furthermore, increased intracellular calcium in TRPM2−/− macrophages enhanced MAPK and NADPH oxidase activities, compared to WT macrophages. Our data suggest that augmented production of ROS and inflammatory cytokines with TRPM2 deletion regulates oxidative stress in macrophages, and consequently, decreases H. pylori gastric colonization while increasing inflammation in the gastric mucosa.