Neurotensin receptor-3/sortilin mediates neurotensin-induced cytokine/chemokine expression in a murine microglial cell line
Neurotensin receptor-3/sortilin mediates neurotensin-induced cytokine/chemokine expression in a murine microglial cell line
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DOI：
10.1002/jnr.20231
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发表时间：
2004-10-01
影响因子：
4.2
通讯作者：
Mazella, J
中科院分区：
文献类型：
--
作者：
Dicou, E;Vincent, JP;Mazella, J
我们表明，I型神经降压素受体-3（也称为分拣蛋白）是唯一已知的神经降压素受体在小鼠小胶质细胞系中表达，其激活导致细胞外信号调节（Erk 1/2）和Akt激酶的磷酸化。利用半定量逆转录酶（RT）PCR，我们证明了神经降压素诱导几种细胞因子/趋化因子的基因表达，包括巨噬细胞炎性蛋白（MIP）-2，单核细胞趋化蛋白（MCP）-1，白细胞介素（IL）-1 β和肿瘤坏死因子（TNF）-α。这种诱导依赖于磷脂酰肌醇3-激酶和促分裂原活化蛋白激酶途径。我们观察到神经降压素对细胞因子/趋化因子表达的影响被神经降压素受体3前肽（该受体的选择性配体）抑制。这些结果表明，神经降压素受体-3在小胶质细胞中是功能性的，其中它介导神经降压素诱导趋化因子/细胞因子表达。(C)2004威利-利斯公司
We show that the type I neurotensin receptor-3 (also called sortilin) is the only known neurotensin receptor expressed in a murine microglial cell line and that its activation leads to phosphorylation of both extracellular signaling-regulated (Erk1/2) and Akt kinases. Using semiquantitative reverse-transcriptase (RT) PCR, we demonstrate that neurotensin induces gene expression of several cytokines/chemokines including macrophage inflammatory protein (MIP)-2, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. This induction is dependent on both phosphatidylinositol 3-kinase and mitogen-activated protein kinases pathways. We observe that the effect of neurotensin on cytokine/chemokine expression is inhibited by the neurotensin receptor-3 propeptide, a selective ligand of this receptor. These results demonstrate that the neurotensin receptor-3 is functional in microglial cells where it mediates the induction of chemokines/cytokines expression by neurotensin. (C) 2004 Wiley-Liss, Inc.