Sphingosine 1-phosphate (S1P) inhibits monocyte-endothelial cell interaction by regulating of RhoA activity.
Recent studies suggest that sphingosine 1-phosphate (S1P) protects against atherosclerosis. We assessed the effects of S1P on monocyte-endothelial interaction in the presence of inflammatory mediators. Pretreatment of THP-1 cells with S1P abolished Phorbol 12 myristate 13-acetate (PMA)-induced THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs). S1P inhibited PMA-induced activation of RhoA, but not PKCs. S1P activated p190Rho GTPase activation protein (GAP) only in the presence of PMA, suggesting an inhibitory effect of S1P and PMA to suppress RhoA. In conclusion, S1P inhibited monocyte-endothelial interactions by inhibiting RhoA activity which may explain its anti-atherogenic effects.
Tani
Mariko
M
Bioethics Research Center, Tokyo Medical and Dental University, 1-5-45, Yushima, Bldg. D-809, Bunkyo-ku, Tokyo 113-8519, Japan.
Kawakami
Akio
A
Nagai
Miyuzu
M
Shimokado
Kentaro
K
Kondo
Kazuo
K
Yoshida
Masayuki
M
D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*