The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock
The neuropeptide neuromedin U promotes IL-6 production from macrophages and endotoxin shock
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DOI：
10.1016/j.bbrc.2006.01.075
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发表时间：
2006-03-24
影响因子：
3.1
通讯作者：
Kojima, M
中科院分区：
文献类型：
--
作者：
Moriyama, M;Matsukawa, A;Kojima, M
Neuromedin U(NMU)是一种神经肽，参与食欲、昼夜节律和原伤害性感觉。然而，NMU受体NMU-R1已被证明在免疫细胞中表达，NMU促进肥大细胞依赖的炎症。在这项研究中，我们证明了NMU在巨噬细胞产生IL-6过程中起着重要作用。NMU缺陷小鼠对盲肠结扎穿孔以及内毒素诱导的感染性休克具有抵抗力。与野生型小鼠相比，经内毒素治疗的NMU缺陷小鼠的IL-6水平显著降低，但未见肿瘤坏死因子-α水平的显著降低。NMU和NMU-R1在野生型巨噬细胞中均有表达，经内毒素处理后，NMU表达上调，而NMU-RI表达下调，而NMU-RI在NMU缺陷的巨噬细胞中未见表达下调，其诱导的IL-6产生严重减少。这些数据表明，内毒素诱导的IL-6表达部分依赖于巨噬细胞中NMU-NMU-R1信号的自分泌/旁分泌激活。(C)2006 Elsevier Inc.保留所有权利。
Neuromedin U (NMU) is a neuropeptide involved in appetite, circadian rhythm, and pronociception. However, the NMU receptor NMU-R1 has been shown to be expressed in immune cells and NMU promotes mast cell-dependent inflammation. In this study, we demonstrated that NMU plays an important role in IL-6 production in macrophages. NMU-deficient mice were resistant against cecal ligation puncture- as well as LPS-induced septic shock. IL-6 but not TNF-alpha levels were markedly reduced in LPS-treated NMU-deficient mice compared with wild type mice. Both NMU and NMU-R1 were expressed in wild type peritoneal macrophages, and treatment with LPS resulted in up-regulation of NMU but down-regulation of NMU-RI expression, however, no down-regulation of NMU-RI was observed in NMU-deficient macrophages where LPS-induced IL-6 production was severely reduced. These data suggest that LPS-induced IL-6 expression is partly dependent on autocrine/paracrine activation of the NMU-NMU-R1 signals in macrophages. (c) 2006 Elsevier Inc. All rights reserved.