Wnt/β-catenin pathway promotes acute lung injury induced by LPS through driving the Th17 response in mice
Wnt/β-catenin pathway promotes acute lung injury induced by LPS through driving the Th17 response in mice
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Wnt/β-catenin 通路通过驱动 Th17 反应促进 LPS 诱导的小鼠急性肺损伤
DOI：
10.1016/j.bbrc.2017.12.058
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发表时间：
2018-01-08
影响因子：
3.1
通讯作者：
Wang, Daoxin
中科院分区：
文献类型：
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作者：
Cheng, Li;Zhao, Yan;Wang, Daoxin
辅助性T细胞17（Th 17）是一种CD 4 + T细胞，在急性肺损伤（ALI）炎症反应中起重要调节作用。近年来的研究表明，Wnt/beta-catenin信号通路可调节CD 4 + T细胞的分化和功能。然而，Wnt/beta-catenin在脂多糖（LPS）诱导的急性肺损伤的发生发展过程中是否能够调控Th 17的分化和功能，目前尚不清楚。为了测试这一点，我们使用dickkopfl（Dkk-1）来阻断Wnt/β-连环蛋白通路，并通过滴注到ALI的鼠模型中使用LiCl来激活Wnt/β-连环蛋白通路。我们的研究结果表明，Wnt/β-catenin通路的激活显著加重LPS诱导的肺部炎症。同时，通过对CD 4（+）T细胞及相关细胞因子分泌的分析，我们观察到Wnt/fi-catenin通路的激活促进了Th 17应答。Th 17反应增强是导致中性粒细胞进一步浸润和促炎细胞因子产生的原因。此外，Wnt/β-连环蛋白途径的激活导致通过组蛋白乙酰转移酶p300诱导视黄酸相关孤儿受体-γ t（RORyt）的表达。提示Wnt/beta-catenin通路可能是治疗LPS诱导的ALI炎症反应的潜在靶点。(C)2017爱思唯尔公司All rights reserved.
T helper cell 17 (Th17), one type of CD4(+) T cell, plays an important role in regulating the acute lung injury (ALI) inflammatory response. Recent studies showed that Wnt/beta-catenin pathway could modulate the differentiation and the function of CD4(+) T cell. However, whether Wnt/beta-catenin could regulate the differentiation and function of Th17 in the development and progress of ALI induced by lipopolysaccharide (LPS) is still unknown. To test this, we used dickkopfl (Dkk-1) to block the Wnt/beta-catenin pathway and LiCI to activate the Wnt/beta-catenin pathway by instillation to the murine model of ALI. Our results revealed that activation of Wnt/beta-catenin pathway significantly aggravated the LPS-induced lung inflammation. Meanwhile, we observed that activation of Wnt/fi-catenin pathway promoted Th17 response by analyzing CD4(+) T cells and the related cytokines secretions. Enhanced Th17 response was responsible for the further neutrophils infiltration and pro-inflammatory cytokines production. In addition, activation of Wnt/beta-catenin pathway resulted in induced expression of retinoic acid related orphan receptor-gamma t (RORyt) via histone acetyltransferase p300. These data suggested that Wnt/beta-catenin pathway might be a potential target to treat the LPS-induced inflammation in ALI. (C) 2017 Elsevier Inc. All rights reserved.