CREB and AP-1 activation regulates MKP-1 induction by LPS or M-CSF and their kinetics correlate with macrophage activation versus proliferation
CREB and AP-1 activation regulates MKP-1 induction by LPS or M-CSF and their kinetics correlate with macrophage activation versus proliferation
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DOI：
10.1002/eji.200839037
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发表时间：
2009-07-01
影响因子：
5.4
通讯作者：
Celada, Antonio
中科院分区：
文献类型：
--
作者：
Casals-Casas, Cristina;Alvarez, Eva;Celada, Antonio
MAPK磷酸酶-1(MKP-1)是一种在天然免疫中起重要作用的蛋白磷酸酶。这种磷酸酶使ERK1/2失活，ERK1/2参与了巨噬细胞两种相反的功能活动，即增殖和激活。我们发现，尽管巨噬细胞的增殖和激活以不同的动力学方式诱导MKP-1，但基因的表达是由位于-380至-180bp之间的近端启动子序列介导的。近端元件的突变实验表明，Cre/AP-1是内毒素或M-CSF诱导MKP-1基因激活所必需的。此外，凝胶位移分析和染色质免疫沉淀结果表明，c-jun和CREB与Cre/AP-1盒结合。M-CSF和LPS表现出的不同动力学与JNK和c-Jun的诱导以及对Raf-1的需求有关。激活MKP-1诱导的信号转导通路与M-CSF和内毒素的诱导具有动力学相关性。
MAPK phosphatase-1 (MKP-1) is a protein phosphatase that plays a crucial role in innate immunity. This phosphatase inactivates ERK1/2, which are involved in two opposite functional activities of the macrophage, namely proliferation and activation. Here we found that although macrophage proliferation and activation induce MKP-1 with different kinetics, gene expression is mediated by the proximal promoter sequences localized between -380 and -180bp. Mutagenesis experiments of the proximal element determined that CRE/AP-1 is required for LPS- or M-CSF-induced activation of the MKP-1 gene. Moreover, the results from gel shift analysis and chromatin immunoprecipitation indicated that c-Jun and CREB bind to the CRE/AP-1 box. The distinct kinetics shown by M-CSF and LPS correlates with the induction of JNK and c-jun, as well as the requirement for Raf-1. The signal transduction pathways that activate the induction of MKP-1 correlate kinetically with induction by M-CSF and LPS.