The uncoupling protein 2 modulates the cytokine balance in innate immunity
The uncoupling protein 2 modulates the cytokine balance in innate immunity
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DOI：
10.1016/j.cyto.2006.07.012
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发表时间：
2006-08-01
期刊：
影响因子：
3.8
通讯作者：
Cassard-Doulcier, Anne-Marie
中科院分区：
文献类型：
--
作者：
Rousset, Sophie;Emre, Yalin;Cassard-Doulcier, Anne-Marie
解偶联蛋白 2 (UCP2) 位于线粒体内膜，下调活性氧 (ROS) 的产生。最近的数据表明 UCP2 在免疫反应中发挥作用。我们在小鼠急性单核细胞增生李斯特菌感染期间进一步分析了这一假设。与Ucp2(+/+)相比，受感染的Ucp2(-/-)小鼠的死亡延迟，这表明UCP2在免疫反应的早期步骤中发挥作用。在体外，Ucp2(-/-)小鼠的较高抵抗力与巨噬细胞更好地控制细菌生长无关。在体内，在 Ucp2(-/-) 小鼠的脾脏中观察到招募的吞噬细胞显着增加。这与脾脏中较高水平的 ROS 有关。感染后4天，在Ucp2(-/-)小鼠中观察到促炎细胞因子IFNγ、IL6和IL1β以及趋化因子MCP1的上调，随后抗炎细胞因子IL10的产生减少。目前的数据强调，在急性感染模型中，UCP2 通过调节 ROS 产生、细胞因子和趋化因子产生以及随后的吞噬细胞招募来调节先天免疫。 (c) 2006 Elsevier Ltd. 保留所有权利。
The uncoupling protein 2 (UCP2) is located in the inner mitochondrial membrane and downregulates the production of reactive oxygen species (ROS). Recent data suggested a role for UCP2 in the immune response. We analyzed further this hypothesis during acute Listeria monocytogenes infection in mice. Death of infected Ucp2(-/-) mice was delayed in comparison with Ucp2(+/+), suggesting a role of UCP2 in the early step of the immune response. In vitro, the higher resistance of Ucp2(-/-) mice was not associated with a better control of bacterial growth by macrophages. In vivo, a significant increase of recruited phagocytes was observed in the spleen of Ucp2(-/-) mice. This was associated with a higher level of ROS in the spleen. Upregulation of pro-inflammatory cytokines IFN gamma, IL6, and IL1 beta and of the chemokine MCP1 was observed in Ucp2(-/-) mice 4 days after infection, preceded by a decrease of the anti-inflammatory cytokine IL10 production. Present data highlight that, in an acute model of infection, UCP2 modulates innate immunity, via the modulation of ROS production, cytokine and chemokine production and consequently phagocyte recruitment. (c) 2006 Elsevier Ltd. All rights reserved.