Functional expression of CCL6 by rat microglia: A possible role of CCL6 in cell-cell communication
Functional expression of CCL6 by rat microglia: A possible role of CCL6 in cell-cell communication
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DOI：
10.1016/j.jneuroim.2005.06.028
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发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Tanaka, J
中科院分区：
文献类型：
--
作者：
Kanno, M;Suzuki, S;Tanaka, J
越来越多的证据表明趋化因子在中枢神经系统（CNS）的免疫监视中起着重要的作用。在中枢神经系统中，小胶质细胞是初级免疫效应细胞，并分泌各种趋化因子以响应其微环境。通过RTPCR和间接免疫荧光分析，我们发现CCL6（在小鼠中称为C10/MRP-1）在没有任何刺激的情况下在大鼠初级小胶质细胞中表达，但在初级星形胶质细胞中不表达，尽管这两种细胞类型都表达CCR1 mRNA，这是CCL6的受体。此外，免疫组织化学分析表明，小胶质细胞在正常大脑中产生CCL6蛋白，这表明小胶质细胞可能是正常大脑中CCL6的主要来源。重组大鼠CCL6在体外介导小胶质细胞和星形胶质细胞的迁移。用pi3激酶抑制剂LY294002处理小胶质细胞可阻断CCL6介导的细胞迁移。Western blot分析显示，重组CCL6处理小胶质细胞可诱导Akt磷酸化，表明CCL6通过激活pi3激酶/Akt通路发挥作用。促炎细胞因子干扰素- γ增强了小胶质细胞中CCL6 mRNA和蛋白的表达，而其他促炎细胞因子白介素-6和肿瘤坏死因子- A以及抗炎细胞因子转化生长因子- β对小胶质细胞中CCL6的表达没有影响。这些发现提示CCL6可能是小胶质细胞在中枢神经系统生理和病理条件下释放的细胞间通讯介质。(C) 2005 Elsevier B.V.版权所有
There is growing evidence that chemokines play important roles in the immune surveillance of central nervous system (CNS). In the CNS, microglia are primary immune effector cells and secrete various chemokines in response to their microenvironment. Using the RTPCR procedure and indirect immunofluorescence analysis, we found that CCL6 (known as C10/MRP-1 in mouse) was expressed in rat primary microglia without any stimulation, but not in primary astrocytes, although both cell types expressed CCR1 mRNA, which is a receptor for CCL6. Furthermore, immumohistochemical analysis demonstrated that microglia produced CCL6 protein in a normal brain, suggesting that microglia may be the primary source of CCL6 in a normal brain. Recombinant rat CCL6 mediated the migration of microglia, and astrocytes in vitro. The CCL6-mediated cell migration was blocked by treating the cells with LY294002, a PI3-kinase inhibitor and Western blot analysis showed that the phosphorylation of Akt could be induced by treating microglia with a recombinant CCL6, suggesting that CCL6 functions by activating the PI3-kinase/Akt pathway. A proinflammatory cytokine, interferon-gamma enhanced the expression of both CCL6 mRNA and protein in microglia, while other proinflammatory cytokines, interleukin-6 and tumor necrosis factor-a and an anti-inflammatory cytokine, transforming growth factor-beta exerted no effect on CCL6 expression in microglia. These findings suggest that CCL6 may be a mediator released by microglia for cell-cell communication under physiological as well as pathological conditions of CNS. (C) 2005 Elsevier B.V. All rights reserved.