Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection.
Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection.
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DOI：
10.1007/s00726-016-2231-2
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发表时间：
2016-10
期刊：
影响因子：
3.5
通讯作者：
Wilson, Keith T.
中科院分区：
文献类型：
--
作者：
Hardbower, Dana M.;Asim, Mohammad;Murray-Stewart, Tracy;Casero, Robert A., Jr.;Verriere, Thomas;Lewis, Nuruddeen D.;Chaturvedi, Rupesh;Piazuelo, M. Blanca;Wilson, Keith T.
我们报道，精氨酸酶 2 (ARG2) 缺失会导致小鼠幽门螺杆菌感染期间胃炎增加并减少细菌负荷。我们的研究暗示了诱导型一氧化氮 (NO) 合酶 (NOS2) 的潜在作用，因为 Arg2−/− 小鼠在胃巨噬细胞中表现出 NOS2 水平升高，并且 NO 可以杀死幽门螺杆菌。我们现在将 Arg2−/− 与 Nos2−/− 小鼠交配，并用幽门螺杆菌感染它们。与野生型小鼠相比，Arg2−/− 和 Arg2−/−;Nos2−/− 小鼠均表现出胃炎增加和定植减少，后者表明 ARG2 缺失对细菌负荷的影响不是由 NO 介导的。虽然 Arg2−/− 小鼠表现出增强的 M1 巨噬细胞活化，但 Nos2−/− 和 Arg2−/−;Nos2−/− 小鼠没有表现出这些变化，但表现出增强的 CXCL1 和 CXCL2 反应。 Arg2−/− 小鼠的胃组织和脾 T 细胞中 Th1/Th17 细胞因子、干扰素 γ 和白细胞介素 17 的表达增加，但 Nos2−/− 或 Arg2−/−;Nos2−/− 小鼠则没有。受感染的 Arg2−/− 小鼠的胃组织表现出精氨酸酶 1、鸟氨酸脱羧酶、腺苷甲硫氨酸脱羧酶 1、亚精胺/精胺 N1-乙酰转移酶 1 和精胺氧化酶表达增加，同时精胺水平增加。这些数据表明，ARG2缺失导致幽门螺杆菌感染期间胃多胺合成和分解代谢的代偿性上调，这可能导致胃部炎症增加和相关的细菌负荷减少。总体而言，本研究的发现是，ARG2 通过限制 M1 巨噬细胞激活和多胺代谢，有助于幽门螺杆菌的免疫逃避。
We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2−/− mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill H. pylori. We now bred Arg2−/− to Nos2−/− mice, and infected them with H. pylori. Compared to wild-type mice, both Arg2−/− and Arg2−/−;Nos2−/− mice exhibited increased gastritis and decreased colonization, the latter indicating that the effect of ARG2 deletion on bacterial burden was not mediated by NO. While Arg2−/− mice demonstrated enhanced M1 macrophage activation, Nos2−/− and Arg2−/−;Nos2−/− mice did not demonstrate these changes, but exhibited increased CXCL1 and CXCL2 responses. There was an increased expression of the Th1/ Th17 cytokines, interferon gamma and interleukin 17, in gastric tissues and splenic T-cells from Arg2−/−, but not Nos2−/− or Arg2−/−;Nos2−/− mice. Gastric tissues from infected Arg2−/− mice demonstrated increased expression of arginase 1, ornithine decarboxylase, adenosylmethionine decarboxylase 1, spermidine/spermine N1-acetyltransferase 1, and spermine oxidase, along with increased spermine levels. These data indicate that ARG2 deletion results in compensatory upregulation of gastric polyamine synthesis and catabolism during H. pylori infection, which may contribute to increased gastric inflammation and associated decreased bacterial load. Overall, the finding of this study is that ARG2 contributes to the immune evasion of H. pylori by restricting M1 macrophage activation and polyamine metabolism.
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阳离子氨基酸转运蛋白2增强了幽门螺杆菌感染期间的先天免疫力。
影响因子：
3.7
作者：
Barry DP;Asim M;Scull BP;Piazuelo MB;de Sablet T;Lewis ND;Coburn LA;Singh K;Ellies LG;Gobert AP;Chaturvedi R;Wilson KT
通讯作者：
Wilson KT
影响因子：
3.5
作者：
Chaturvedi R;de Sablet T;Coburn LA;Gobert AP;Wilson KT
通讯作者：
Wilson KT
影响因子：
2.3
作者：
Bonequi, Patricia;Meneses-Gonzalez, Fernando;Correa, Pelayo;Rabkin, Charles S.;Constanza Camargo, M.
通讯作者：
Constanza Camargo, M.
影响因子：
3.7
作者：
Coburn, Lori A.;Horst, Sara N.;Wilson, Keith T.
通讯作者：
Wilson, Keith T.
影响因子：
4.4
作者：
Gobert, AP;Cheng, YL;Wilson, KT
通讯作者：
Wilson, KT