Suppression of the lipopolysaccharide-induced expression of MARCKS-related protein (MRP) affects transmigration in activated RAW264.7 cells

Suppression of the lipopolysaccharide-induced expression of MARCKS-related protein (MRP) affects transmigration in activated RAW264.7 cells
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DOI:
10.1016/j.cellimm.2009.01.011
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发表时间:
2009-01-01
影响因子:
4.3
通讯作者:
Lee, Won-Ha
Lee, Won-Ha
中科院分区:
医学4区
文献类型:
--
作者:
Chun, Kwang-Rok;Bae, Eun Mi;Lee, Won-Ha

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MRP是蛋白激酶C(PKC)的底物之一,其分子作用机制一直受到广泛的研究,但其在巨噬细胞功能中的作用仍存在争议。用细菌脂多糖(LPS)处理巨噬细胞系诱导高水平的MRP表达,表明MRP在活化的巨噬细胞的功能中起作用。为了研究MRP在活化RAW264.7细胞中的作用,我们稳定转染MRP特异性shRNA表达构建体,并测试巨噬细胞相关功能的改变。MRP表达的下调导致对MCP-1或细胞外基质蛋白的趋化性显著降低。此外,PKC的药理学抑制剂显著抑制RAW264.7细胞的趋化性。这些数据揭示了MRP在活化的RAW 264.7细胞的迁移中的关键作用。(C)2009爱思唯尔公司All rights reserved.
The molecular action mechanism of MRP, one of the protein kinase C (PKC) substrates, has been under intense investigation, but reports on its role in macrophage function remain controversial. The treatment of macrophage cell lines with bacterial lipopolysaccharide (LPS) induced a high level of MRP expression suggesting that MRP plays a role in the function of activated macrophages. In order to investigate the role of MRP in activated RAW264.7 cells, we stably transfected MRP-specific shRNA expression constructs and tested for alterations in macrophage-related functions. The down-regulation of MRP expression resulted in a marked reduction in chemotaxis toward MCP-1 or extracellular matrix proteins. Furthermore, pharmacological inhibitors of PKC significantly inhibited the chemotaxis in RAW264.7 cells. These data reveals the pivotal role of MRP in the transmigration of activated RAW264.7 cells. (C) 2009 Elsevier Inc. All rights reserved.