HSF1 Attenuates LPS-Induced Acute Lung Injury in Mice by Suppressing Macrophage Infiltration.

HSF1 Attenuates LPS-Induced Acute Lung Injury in Mice by Suppressing Macrophage Infiltration.
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HSF1 通过抑制巨噬细胞浸润减轻 LPS 引起的小鼠急性肺损伤

DOI:
10.1155/2020/1936580
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发表时间:
2020
影响因子:
--
通讯作者:
Xiao X
Xiao X
中科院分区:
生物学2区
文献类型:
--
作者:
Li T;Xiao G;Tan S;Shi X;Yin L;Tan C;Gu J;Liu Y;Deng H;Liu K;Liu M;Zhang H;Xiao X

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热休克因子1(HSF1)是一种参与热休克反应等生物过程的转录因子。我们在这里揭示了HSF1在急性肺损伤(ALI)中的重要作用。以HSF1基因敲除小鼠作为脂多糖(LPS)诱导的ALI模型。与−/−+/+组相比,HSF1+/+组小鼠肺损伤加重,肺泡灌洗液和肺组织中巨噬细胞浸润明显增加。经脂多糖刺激后,−/−小鼠血清、肺泡灌洗液和肺组织中单核细胞趋化蛋白-1水平明显高于HSF1+/+组,巨噬细胞表面单核细胞趋化蛋白-1和趋化因子(C-C基序)受体2的表达也明显高于HSF1+/+组。凝胶迁移率改变分析(EMSA)和双荧光素酶报告分析表明,HSF1可以直接与MCP-1及其受体CCR2启动子区域的热休克元件(HSE)结合,从而抑制这两个基因的表达。结论:HSF1通过直接抑制MCP-1/CCR2的转录,从而减少巨噬细胞的浸润,从而减轻了内毒素诱导的小鼠ALI。
Heat shock factor 1 (HSF1) is a transcription factor involved in the heat shock response and other biological processes. We have unveiled here an important role of HSF1 in acute lung injury (ALI). HSF1 knockout mice were used as a model of lipopolysaccharide- (LPS-) induced ALI. Lung damage was aggravated, and macrophage infiltration increased significantly in the bronchoalveolar lavage fluid (BALF) and lung tissue of HSF−/− mice compared with the damage observed in HSF1+/+ mice. Upon LPS stimulation, HSF−/− mice showed higher levels of monocyte chemoattractant protein-1 (MCP-1) in the serum, BALF, and lung tissue and increased the expression of MCP-1 and chemokine (C-C motif) receptor 2 (CCR2) on the surface of macrophages compared with those in HSF1+/+. Electrophoretic mobility shift assays (EMSA) and dual luciferase reporter assays revealed that HSF1 could directly bind to heat shock elements (HSE) in the promoter regions of MCP-1 and its receptor CCR2, thereby inhibiting the expression of both genes. We concluded that HSF1 attenuated LPS-induced ALI in mice by directly suppressing the transcription of MCP-1/CCR2, which in turn reduced macrophage infiltration.
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