MCP-1-stimulated chemotaxis of monocytic and endothelial cells is dependent on activation of different signaling cascades
MCP-1-stimulated chemotaxis of monocytic and endothelial cells is dependent on activation of different signaling cascades
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DOI：
10.1016/j.cyto.2005.06.016
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发表时间：
2005-09-21
期刊：
影响因子：
3.8
通讯作者：
Krasnikova, TL
中科院分区：
文献类型：
--
作者：
Arefieva, TI;Kukhtina, NB;Krasnikova, TL
单核细胞趋化蛋白-1(MCP-1)在将单核细胞吸引到炎症部位起重要作用。MCP-I除了能诱导单核细胞募集外，还能影响内皮细胞的趋化反应。MCP-1诱导细胞迁移的分子机制尚不清楚。在目前的研究中，我们证实了单核细胞和内皮细胞在MCP-1刺激下，p42/44(ERK1/2)和p38丝裂原激活蛋白激酶(MAPKs)、磷脂酰二肌醇-3-激酶(PI3K)和Src-Kase被激活。MCP-1刺激后3min内即可检测到该反应，且反应迅速且具有时间依赖性。PI3K抑制剂LY294002可部分阻断MCP-I诱导的p42/44(Erki/2)MAPK的磷酸化，而Src-Kinase抑制剂PP2对p38 MAPK的磷酸化有较大程度的抑制作用。P38MAPK抑制剂对单核细胞迁移有明显的抑制作用，而对p42/44(Erki/2)MAPK活性的抑制作用不明显。相反，PI3K和p42/44(Erki/2)抑制剂可完全阻断MCP-I刺激内皮细胞的趋化作用，而p38 MAPK抑制剂则不能。这些结果表明，MCP-1激活了平行的信号转导通路，并且根据细胞类型的不同，这些通路对细胞趋化活性的贡献是不同的。(C)2005爱思唯尔有限公司。保留所有权利。
Monocyte chemoattractant protein-1 (MCP-1) is important in attracting monocytes to sites of inflammation. Besides induction of monocyte recruitment, MCP- I can also affect chemotactic response of endothelial cells. The molecular mechanisms involved in MCP-1-induced cell migration are poorly understood. In the current investigation, we demonstrate activation of p42/44(ERK1/2) and p38 mitogen-activated protein kinases (MAPKs), phosphatydilinositol-3-kinase (PI3K) and Src-kinases in both monocytes and endothelial cells stimulated with MCP-1 in vitro. The response was rapid and time-dependent, detectable within 3 min of MCP-1 stimulation. MCP- I -induced phosphorylation of p42/44(ERKI/2) MAPKs was partially blocked by inhibitor of PI3K LY294002, while phosphorylation of p38 MAPK was diminished to a greater extent in presence of Src-kinase inhibitor PP2. There was a substantial inhibition of monocyte migration upon treatment with inhibitors of p38 MAPK, at the same time inhibition of p42/44(ERKI/2) MAPK activation had no effect. On the contrary, the MCP- I -stimulated chemotaxis of endothelial cells was completely abolished by inhibitors of PI3K and p42/44(ERKI/2), but not by p38 MAPK inhibitors. These results suggest that parallel signal transduction pathways are activated by MCP-1, and that depending on the cell type these pathways differentially contribute to cell chemotactic activity. (c) 2005 Elsevier Ltd. All rights reserved.