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.docVIP

  SphK1/S1P/S1PR1 signaling stimulates cell migration in RAW264.7 macrophages# Li Changyong* 5 10 15 20 (Department of Physiology, Wuhan University, WuHan 430071) 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 25 0 Introduction Macrophages are versatile hematopoietic cells that fulfil manifold tasks in the imm