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-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 Gα(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 Gα(q)-dependent mechanism both possibly through the S1P(2) receptors. © 2005 Elsevier Inc. All rights reserved.