ATF-2 regulates lipopolysaccharide-induced transcription in macrophage cells.
ATF-2 regulates lipopolysaccharide-induced transcription in macrophage cells.
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DOI：
10.1016/j.bbrc.2009.05.001
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发表时间：
2009-07
影响因子：
3.1
通讯作者：
N. Hirose;T. Maekawa;T. Shinagawa;S. Ishii
中科院分区：
文献类型：
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作者：
N. Hirose;T. Maekawa;T. Shinagawa;S. Ishii
转录因子ATF-2是ATF/CREB家族成员之一，是p38的靶标，参与应激诱导的细胞凋亡和Toll样受体(TLR)介导的信号转导。用脂多糖、MALP-2或CpG-ODN处理RAW264.7巨噬细胞后，ATF-2在Thr-71处的磷酸化程度增加。脂多糖处理可增强ATF-2的反式激活能力。在内毒素诱导的多种基因中，ATF-2 siRNA处理RAW264.7细胞可显著降低内毒素诱导的SOCS-3的表达。ATF-2和LPS协同刺激SOCS-3启动子转录，而ATF-2 siRNA抑制SOCS-3启动子转录。组蛋白脱乙酰酶1(HDAC1)在内毒素处理后与ATF-2相互作用，但在处理前不能。用HDAC的抑制剂曲古抑素A处理RAW264.7细胞，可抑制内毒素诱导的SOCS-3的表达，提示HDAC1正向调节内毒素诱导的SOCS-3的转录。因此，ATF-2在TLR介导的巨噬细胞转录调控中起重要作用。
The transcription factor ATF-2, a member of the ATF/CREB family, is a target of p38 that are involved in stress-induced apoptosis and in Toll-like receptor (TLR)-mediated signaling. Phosphorylation of ATF-2 at Thr-71 was enhanced by treating of RAW264.7 macrophage cells with either LPS, MALP-2, or CpG-ODN. LPS treatment enhanced the trans-activation capacity of ATF-2. Among multiple LPS-induced genes, the LPS-induced expression of Socs-3 was significantly reduced by the treatment of RAW264.7 cells with an Atf-2 siRNA. Transcription from the Socs-3 promoter was synergistically stimulated by ATF-2 and LPS, whereas it was suppressed by Atf-2 siRNA. Histone deacetylase 1 (HDAC1) interacted with ATF-2 after LPS treatment, but not before treatment. Treatment of RAW264.7 cells with trichostatin A, an inhibitor of HDAC, suppressed the LPS-induced Socs-3 expression, suggesting that HDAC1 positively regulates the LPS-induced transcription of Socs-3. Thus, ATF-2 plays an important role in TLR-mediated transcriptional control in macrophage cells.