Sphingosine 1-Phosphate (S1P)/S1P Receptor2/3 Axis Promotes Inflammatory M1 Polarization of Bone Marrow-Derived Monocyte/Macrophage via G(α)i/o/PI3K/JNK Pathway
Sphingosine 1-Phosphate (S1P)/S1P Receptor2/3 Axis Promotes Inflammatory M1 Polarization of Bone Marrow-Derived Monocyte/Macrophage via G(α)i/o/PI3K/JNK Pathway
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1-磷酸鞘氨醇 (S1P)/S1P 受体 2/3 轴通过 G(α)i/o/PI3K/JNK 途径促进骨髓源性单核细胞/巨噬细胞的炎症 M1 极化
DOI：
10.1159/000493611
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发表时间：
2018-09
影响因子：
--
通讯作者：
Liying Li
中科院分区：
文献类型：
--
作者：
Jingjing Yang;Le Yang;Lei Tian;Xiaofang Ji;Lin Yang;Liying Li
Background/Aims: Macrophages, the most plastic cells in the haematopoietic system, are found in all tissues and show great functional heterogeneity. Sphingosine 1-phosphate (S1P)/ S1P receptors (S1PRs) system is widely involved in the process of inflammatory disease, whereas little evidence concerning its role in functional macrophage polarization is available. Thus, the present study was designed to evaluate the effects of S1P/S1PRs on functional polarization of macrophage in mouse bone marrow (BM)-derived monocyte/macrophages (BMMs). Methods: For the detection of M1 macrophage markers, such as CD86, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1/ chemokine (C-C motif) ligand (CCL) 2, nitric oxide synthase (NOS) 2, and macrophage inflammatory protein (MIP)-1β, RT-qPCR and cytometric bead array (CBA) were performed in cultured primary BMMs after the treatment with selective S1PR2/3 antagonists or specific S1PRs siRNA. Western blotting and immunofluorescence were used for the detection of phosphorylation of JNK1/2. Results: BMMs expressed S1PR1-3 and interestingly, S1PR2/3, but not S1PR1, mediates S1P-induced M1 macrophage polarization of BMMs as their siRNA or antagonists reduced M1 genes’ expression. We found that PTX (inhibitor of G(α)i/o), LY294002 (inhibitor of PI3K) or SP600125 (inhibitor of JNK1/2) prevented up-regulation of M1 genes expression mediated by S1P/S1PR2/3 signal, and S1P-induced JNK phosphorylation was inhibited by antagonists of S1PR2/3, PTX or LY294002. Conclusion: Collectively, our results demonstrate that S1P/S1PR2/3 plays a key role in regulating M1 type polarization of BMMs and acts by activating G(α)i/o/PI3K/JNK signaling pathway, with potential implications for new approaches to inflammatory liver disease therapy.
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影响因子：
13.5
作者：
Sica, Antonio;Invernizzi, Pietro;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
影响因子：
25.7
作者：
Li, Changyong;Kong, Yaxian;Li, Liying
通讯作者：
Li, Liying
1-磷酸鞘氨醇受体 2 和 3 介导小鼠胆汁淤积性肝损伤中骨髓源性单核细胞/巨噬细胞的运动
影响因子：
4.6
作者：
Yang L;Han Z;Tian L;Mai P;Zhang Y;Wang L;Li L
通讯作者：
Li L
泛素连接酶 praja2 对 MFHAS1 的泛素化通过激活 JNK 和 p38 途径促进 M1 巨噬细胞极化
影响因子：
9
作者：
Zhong J;Wang H;Chen W;Sun Z;Chen J;Xu Y;Weng M;Shi Q;Ma D;Miao C
通讯作者：
Miao C
影响因子：
4.6
作者：
Aoki M;Aoki H;Ramanathan R;Hait NC;Takabe K
通讯作者：
Takabe K