CCL2/MCP-1 modulation of microglial activation and proliferation.
CCL2/MCP-1 modulation of microglial activation and proliferation.
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DOI：
10.1186/1742-2094-8-77
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发表时间：
2011-07-05
影响因子：
9.3
通讯作者：
Madrigal JL
中科院分区：
文献类型：
--
作者：
Hinojosa AE;Garcia-Bueno B;Leza JC;Madrigal JL
单核细胞趋化蛋白（CCL2/MCP - 1）是一种趋化因子，能吸引参与免疫/炎症反应的细胞。由于小胶质细胞是维持脑部炎症的主要细胞类型之一，我们在此提出分析MCP - 1对原代培养小胶质细胞的直接作用。
原代小胶质细胞和神经元培养物分别取自新生和胚胎期的Wistar大鼠。小胶质细胞与不同浓度的重组MCP - 1和脂多糖（LPS）一起孵育。通过测量溴脱氧尿苷（BrdU）的掺入量来量化细胞增殖。使用格里斯试剂检测亚硝酸盐的积累。通过逆转录聚合酶链反应（RT - PCR）和酶联免疫吸附测定（ELISA）测量不同蛋白质的表达和合成。通过测量乳酸脱氢酶（LDH）释放到培养基中的量来量化细胞死亡。
MCP - 1处理（50 ng/ml，24小时）未引起小胶质细胞培养物的形态变化。对不同细胞因子的蛋白质和信使核糖核酸（mRNA）水平进行了测量，结果表明MCP - 1自身或与LPS联合都不能诱导促炎细胞因子（白细胞介素 - 1β、白细胞介素6、巨噬细胞炎性蛋白 - 1α）的产生。在测量诱导型一氧化氮合酶（NOS2）的表达或培养基中亚硝酸盐的积累（作为小胶质细胞激活的不同指标）时，也观察到了类似的无效应情况。MCP - 1也不能改变因LPS处理而减少的不同营养因子的表达。为了探究小胶质细胞可能释放的其他产物及其潜在的神经毒性，将神经元与小胶质细胞共培养：用MCP - 1处理时未检测到神经元死亡。然而，MCP - 1的存在会诱导小胶质细胞增殖，这一效应与LPS所观察到的相反。
这些数据表明，虽然MCP - 1会引起小胶质细胞的迁移和增殖，但它似乎不会直接激活这种细胞类型的炎症反应，因此，可能需要其他因素来引起在MCP - 1水平升高的情况下常见的神经元损伤相关变化。
Monocyte chemoattractant protein (CCL2/MCP-1) is a chemokine that attracts cells involved in the immune/inflammatory response. As microglia are one of the main cell types sustaining inflammation in brain, we proposed here to analyze the direct effects of MCP-1 on cultured primary microglia. Primary microglia and neuronal cultures were obtained from neonatal and embryonic Wistar rats, respectively. Microglia were incubated with different concentrations of recombinant MCP-1 and LPS. Cell proliferation was quantified by measuring incorporation of bromodeoxyuridine (BrdU). Nitrite accumulation was measured using the Griess assay. The expression and synthesis of different proteins was measured by RT-PCR and ELISA. Cell death was quantified by measuring release of LDH into the culture medium. MCP-1 treatment (50 ng/ml, 24 h) did not induce morphological changes in microglial cultures. Protein and mRNA levels of different cytokines were measured, showing that MCP-1 was not able to induce proinflammatory cytokines (IL-1β, IL6, MIP-1α), either by itself or in combination with LPS. A similar lack of effect was observed when measuring inducible nitric oxide synthase (NOS2) expression or accumulation of nitrites in the culture media as a different indicator of microglial activation. MCP-1 was also unable to alter the expression of different trophic factors that were reduced by LPS treatment. In order to explore the possible release of other products by microglia and their potential neurotoxicity, neurons were co-cultured with microglia: no death of neurons could be detected when treated with MCP-1. However, the presence of MCP-1 induced proliferation of microglia, an effect opposite to that observed with LPS. These data indicate that, while causing migration and proliferation of microglia, MCP-1 does not appear to directly activate an inflammatory response in this cell type, and therefore, other factors may be necessary to cause the changes that result in the neuronal damage commonly observed in situations where MCP-1 levels are elevated.
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影响因子：
3.3
作者：
Melik-Parsadaniantz, Stephane;Rostene, William
通讯作者：
Rostene, William
DOI：
10.1016/s0169-328x(02)00158-4
发表时间：
2002-06-30
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Muessel, MJ;Klein, RM;Berman, NEJ
通讯作者：
Berman, NEJ
影响因子：
4.2
作者：
Kalinin, Sergey;Gavrilyuk, Vitaliy;Feinstein, Douglas L.
通讯作者：
Feinstein, Douglas L.
影响因子：
5.3
作者：
Belmadani, A;Tran, PB;Miller, RJ
通讯作者：
Miller, RJ
影响因子：
6.6
作者：
Madrigal, Jose L. M.;Dello Russo, Cinzia;Feinstein, Douglas L.
通讯作者：
Feinstein, Douglas L.