Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells

Tadayoshi Kawata, Tamotsu Ishizuka, Hideaki Tomura, Takeshi Hisada, Kunio Dobashi, Hideo Tsukagoshi, Mitsuteru Ishiwara, Hitoshi Kurose, Masatomo Mori, Fumikazu Okajima

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Sphingosine 1-phosphate (S1P), a bioactive lipid mediator, has been shown to be increased in bronchoalveolar lavage fluid after allergen challenge in asthmatic patients. Here, we examined S1P actions and their intracellular signalings in cultured human bronchial smooth muscle cells (BSMCs). Expression of mRNAs of three subtypes of S1P receptors, including S1P1, S1P 2, and S1P3, was detected in BSMCs, and exposure of the cells to S1P inhibited platelet-derived growth factor (PDGF)-induced migration and tumor necrosis factor-α-induced RANTES production. S1P also inhibited PDGF-induced Rac1 activation, and dominant negative Rac1 inhibited PDGF-induced migration. On the other hand, dominant negative Gαq attenuated the S1P-induced inhibition of RANTES production. Finally, an S1P 2-selective antagonist, JTE-013, suppressed the S1P-induced inhibition of migration response and RANTES production. These results suggest that S1P attenuates cell migration by inhibiting a Rac1-dependent signaling pathway and decreases RANTES production by stimulating a Gαq- dependent mechanism both possibly through the S1P2 receptors.

Original languageEnglish
Pages (from-to)640-647
Number of pages8
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Jun 3 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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