SIRT1 regulates inflammation response of macrophages in sepsis mediated by long noncoding RNA
SIRT1 regulates inflammation response of macrophages in sepsis mediated by long noncoding RNA
复制标题
SIRT1 调节脓毒症中长非编码 RNA 介导的巨噬细胞炎症反应
DOI：
10.1016/j.bbadis.2017.12.029
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发表时间：
2018-03-01
影响因子：
6.2
通讯作者：
Hu, Dahai
中科院分区：
文献类型：
--
作者：
Jia, Yanhui;Li, Zhenzhen;Hu, Dahai
脓毒症期间SIRT 1调节巨噬细胞免疫应答的分子机制尚不清楚。在这里，我们发现SIRT 1表达下调巨噬细胞从小鼠脓毒症模型或LPS刺激。巨噬细胞中的SIRT 1表达与低水平的长非编码RNA（lncRNA）-NONMMUT 003701 [命名为lncRNA-CCL 2]相关。SIRT 1通过维持lncRNA-CCL 2基因座中的抑制性染色质状态来抑制lncRNA-CCL 2表达。通过敲低lncRNA-CCL 2下调炎症细胞因子表达。这种抑制可以通过SIRT 1活性的降低而部分逆转。因此，这项工作揭示了以前未确定的机制，其中SIRT 1与lncRNA和lncRNA调节巨噬细胞炎症反应。
Molecular mechanisms for macrophage immune responses modulated by SIRT1 during sepsis remain unclear. Here, we show that SIRT1 expression is down-regulated in macrophages from mouse sepsis model or LPS stimulation. SIRT1 expression in macrophages correlates with low levels of a long noncoding RNA (lncRNA)-NONMMUT003701 [named as lncRNA-CCL2]. SIRT1 inhibits lncRNA-CCL2 expression via sustaining a repressive chromatin state in the lncRNA-CCL2 locus. The inflammation cytokines expression is downregulated by knockdown of lncRNA-CCL2. Such inhibition can be reversed partly by decreased SIRT1 activity. Thus, this work uncovers previously unidentified mechanisms in which SIRT1 associates with lncRNA and lncRNA regulates macrophage inflammatory response.