Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells.
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 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 Galpha(q) 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 Galpha(q)-dependent mechanism both possibly through the S1P(2) receptors.
Kawata
Tadayoshi
T
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi 371-8511, Japan.
Ishizuka
Tamotsu
T
Tomura
Hideaki
H
Hisada
Takeshi
T
Dobashi
Kunio
K
Tsukagoshi
Hideo
H
Ishiwara
Mitsuteru
M
Kurose
Hitoshi
H
Mori
Masatomo
M
Okajima
Fumikazu
F
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000235:genetics; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D018946:Chemokine CCL5; D008246:Lysophospholipids; D016328:NF-kappa B; D010982:Platelet-Derived Growth Factor; D049349:Receptors, Lysosphingolipid; D014409:Tumor Necrosis Factor-alpha; C060506:sphingosine 1-phosphate; D048031:JNK Mitogen-Activated Protein Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020830:rac1 GTP-Binding Protein; D013110:Sphingosine