Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells
Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells
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DOI：
10.1016/j.bbrc.2005.03.223
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发表时间：
2005-06-03
影响因子：
3.1
通讯作者：
Okajima, F
中科院分区：
文献类型：
--
作者：
Kawata, T;Ishizuka, T;Okajima, F
1-磷酸鞘氨醇（S1 P）是一种生物活性的脂质介质，在哮喘患者变应原激发后，其含量增加。这里.我们在培养的人支气管平滑肌细胞（BSMCs）中检测了SIP的作用及其细胞内信号传导。S1 P受体3种亚型（S1 P（1）、S1 P（2）和S1 P（3））的mRNA在BSMCs中均有表达。并且细胞暴露于S1 P抑制血小板衍生生长因子（PDGF）诱导的迁移和肿瘤坏死因子-α诱导的RANTES产生。S1 P还抑制PDGF诱导的Rac 1激活，显性负Rac 1抑制PDGF诱导的迁移。另一方面，显性负性G alpha（q）减弱了S1 P诱导的RANTES产生抑制。最后，S1 P选择性拮抗剂JTE-013抑制S1 P诱导的迁移反应和RANTES产生的抑制。这些结果表明，SIP通过抑制Rac 1依赖性信号通路减弱细胞迁移，并通过刺激G α（q）依赖性机制减少RANTES的产生，两者都可能通过S1 P（2）受体。(c)2005年爱思唯尔公司All rights reserved.
Sphingosine 1-phosphate (S1P), a bioactive lipid mediator, has been shown to be increased in la age fluid after allergen challenge in asthmatic patients. Here. we examined SIP actions and their intracellular signallings in cultured human bronchial smooth muscle cells (BSMCs). Expression of mRNAs of three subtypes of S1P receptors, including S1P(1), S1P(2), and S1P(3), was detected in BSMCs. and exposure of the cells to S1P inhibited platelet-derived growth factor (PDGF)-induced migration and tumor necrosis factor-alpha-induced RANTES production. S1P also inhibited PDGF-induced Rac1 activation, and dominant negative Rac1 inhibited PDGF-induced migration. On the other hand, dominant negative G alpha(q) attenuated the S1P-induced inhibition of RANTES production. Finally, an S1P-selective antagonist, JTE-013, suppressed the S1P-induced inhibition of migration response and RANTES production. These results suggest that SIP attenuates cell migration by inhibiting a Rac1-dependent signaling pathway and decreases RANTES production by stimulating a G alpha(q)-dependent mechanism both possibly through the S1P(2) receptors. (c) 2005 Elsevier Inc. All rights reserved.