Tani Mariko, Kawakami Akio, Nagai Miyuzu, Shimokado Kentaro, Kondo Kazuo, Yoshida Masayuki
Bioethics Research Center, Tokyo Medical and Dental University, 1-5-45, Yushima, Bldg. D-809, Bunkyo-ku, Tokyo 113-8519, Japan.
FEBS Lett. 2007 Oct 2;581(24):4621-6. doi: 10.1016/j.febslet.2007.08.053. Epub 2007 Aug 31.
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.
近期研究表明，1-磷酸鞘氨醇（S1P）可预防动脉粥样硬化。我们评估了在存在炎症介质的情况下S1P对单核细胞与内皮细胞相互作用的影响。用S1P预处理THP-1细胞可消除佛波酯（PMA）诱导的THP-1细胞与人脐静脉内皮细胞（HUVECs）的黏附。S1P抑制PMA诱导的RhoA激活，但不抑制蛋白激酶C（PKCs）。S1P仅在存在PMA的情况下激活p190Rho GTP酶激活蛋白（GAP），表明S1P和PMA具有抑制RhoA的作用。总之，S1P通过抑制RhoA活性来抑制单核细胞与内皮细胞的相互作用，这可能解释了其抗动脉粥样硬化的作用。
