鞘氨醇激酶-1/磷酸鞘氨醇受体-1信号轴介导RAW264.7巨噬细胞迁移的作用机制SphK1/S1P/S1PR1 signaling stimulates cell migration in RAW264.7 macrophages

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方法:通过体外细胞迁移实验探讨磷酸鞘氨醇(S1P)对巨噬细胞的迁移作用

本研究充分证明了S1P通过其S1PR1受体介导了小鼠巨噬细胞系RAW264

7的迁移

) 摘要: 目的:探讨磷酸鞘氨醇信号系统对巨噬细胞迁移的影响

采用RNA干扰技术和受体拮抗剂分析参与巨噬细胞迁移的S1P受体类型

TGF-β1显著上调了鞘氨醇激酶1(SphK1)的表达以及S1P的产生

结果:S1P明显刺激了小鼠巨噬细胞系RAW264

7细胞的迁移

磷酸鞘氨醇

) Abstract: Macrophage recruitment to sites of inflammation is an essential step in host defense

However, the signals regulating the mobilization of these cells are still not fully understood

Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, is known to regulate an array of biological activities in various cell types

Here, we investigated the roles of S1P and S1P receptors (S1PRs) in macrophage migration in vitro

Furthermore, we explored the cross-talk between transforming growth factor-β1 (TGF-β1) and S1P signaling pathways in this process

We found that S1P exerted a powerful migratory action on RAW264

7 macrophages, as determined in Boyden chambers

Moreover, by employing RNA interference technology and pharmacological tools, we have demonstrated that S1PR1, but not S1PR2 and S1PR3, is required for S1P-induced macrophage migration

Importantly, we observed a pronounced increase in sphingosine kinase 1 (SphK1) mRNA expression and subsequently increase in S1P production, following transforming growth factor-β1 (TGF-β1) stimulation in RAW264

7 macrophages

The expression of S1PR1, but not S1PR2 and S1PR3, was also significantly up-regulated after TGF-β1 stimulation

Interestingly, exogenously added S1P induced up-regulation of SphK1 and the synthesis of additional S1P, suggesting a self-amplifying loop of S1P to enhance macrophage migration

In conclusion, our results reveal that SphK1/S1PR1 signalling axis is induced by TGF-β1 and stimulates cell migration in RAW 264

7 macrophages

This study provides new clues for the molecular mechanisms of macrophage recruitment during inflammation

Keywords: Sphingosine kinase 1; Sphingosine-1-phosphate; TGF-β1; Cell migration; Macrophages 下载PDF阅读器 PDF全文下载: 初稿 ( 237 ) 作者简介: Li Changyong, (1979-), male, lecturer, liver diseases

通信联系人: 【收录情况】 中国科技论文在线: 李长勇

 鞘氨醇激酶-1/磷酸鞘氨醇受体-1信号轴介导RAW264

7巨噬细胞迁移的作用机制[EB/OL]

北京:中国科技论文在线

还发现外源性的S1P上调了RAW264

7细胞中SphK1的表达

鞘氨醇激酶

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