Wnt/β-catenin signaling regulates lipopolysaccharide-altered polarizations of RAW264.7 cells and alveolar macrophages in mouse lungs

Wnt/β-catenin signaling regulates lipopolysaccharide-altered polarizations of RAW264.7 cells and alveolar macrophages in mouse lungs
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Wnt/β-连环蛋白信号调节脂多糖改变小鼠肺中 RAW264.7 细胞和肺泡巨噬细胞的极化

DOI:
10.1177/20587392211059362
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发表时间:
2021-01
影响因子:
0.7
通讯作者:
Xiaoming Liu
Xiaoming Liu
中科院分区:
医学4区
文献类型:
--
作者:
Jiali Yang;Ying Wang;D;an Yang;Jia Ma;Shuang Wu;Qian Cai;Jing Xue;Chao Yuan;Jing Wang;Xiaoming Liu

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前言巨噬细胞能够在不同的环境刺激下发挥促炎和抗炎功能,分别分化为典型的炎症状态(M1)和抗炎表型(M2)。Wnt/β-Catenin信号在组织内稳态和免疫调节中发挥重要作用,包括巨噬细胞极化。然而,Wnt/β-catenin信号在炎症状态下调节肺泡巨噬细胞极化的分子机制尚不清楚。方法采用免疫印迹和免疫染色方法检测Wnt/β-catenin信号转导的小鼠巨噬细胞样RAW264.7细胞和体内肺泡巨噬细胞在幼稚和脂多糖诱导的炎症状态下的表型变化。结果在幼稚状态下,Wnt/β-catenin信号通路的激活抑制巨噬细胞M1极化,但促进交替M2极化。有趣的是,在脂多糖诱导的炎症条件下,增强的Wnt/β-catenin活性在体外抑制了RAW264.7细胞的M1和M2极化,在体内抑制了内毒素攻击的小鼠原代肺泡巨噬细胞的M1和M2极化。分子分析进一步证明Stat Signal参与调节Wnt/β-Catenin信号改变的小鼠肺泡巨噬细胞极化。结论WNT/β-连环蛋白信号通路可能通过调节STAT信号通路来调节炎症状态下巨噬细胞的极化。
Introduction Macrophages are capable of exerting both proinflammatory and anti-inflammatory functions in response to distinct environmental stimuli, by polarizing into classically inflammatory state (M1) and anti-inflammatory phenotype (M2), respectively. The Wnt/β-catenin signaling plays an important role in the tissue homeostasis and immune regulations, including the macrophage polarizations. However, the molecular mechanism of Wnt/β-catenin signaling in regulating alveolar macrophage polarization in an inflammatory state remains unclear. Methods The Wnt/β-catenin signaling-altered phenotypes of murine macrophage-like RAW264.7 cells in vitro and alveolar macrophage in vivo in both of naïve and lipopolysaccharide-induced inflammation states were accessed by immunoblotting and immunostaining assays. Results The activation of Wnt/β-catenin signaling inhibited macrophage M1 polarization, but promoted alternative M2 polarization in murine RAW264.7 cells under a naïve state. Interestingly, in an LPS-induced inflammation condition, the enhanced Wnt/β-catenin activity suppressed both M1 and M2 polarizations in RAW264.7 cells in vitro, and primary alveolar macrophages of LPS-challenged mice in vivo. Molecular analysis further demonstrated an involvement of Stat signing in regulating Wnt/β-catenin signaling-altered polarizations in mouse alveolar macrophages. Conclusion These results suggest a mechanism by which Wnt/β-catenin signaling modulates macrophage polarization in an inflammation state by regulating the Stat signaling pathway.
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发表时间: 2010-04
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