Sphingosine 1-phosphate receptors mediate stimulatory and inhibitory signalings for expression of adhesion molecules in endothelial cells
Sphingosine 1-phosphate receptors mediate stimulatory and inhibitory signalings for expression of adhesion molecules in endothelial cells
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DOI：
10.1016/j.cellsig.2005.07.011
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发表时间：
2006-06-01
影响因子：
4.8
通讯作者：
Okajima, F
中科院分区：
文献类型：
--
作者：
Kimura, T;Tomura, H;Okajima, F
磷酸鞘氨醇（SlP）刺激人脐静脉内皮细胞血管细胞粘附分子-1和细胞间粘附分子-1的表达。SlP诱导的作用与核因子κ B活化有关，并被百日咳毒素以及SlP受体特异性反义寡核苷酸抑制，尤其是SlP（3）。SlP还刺激内皮型一氧化氮合酶（eNOS），其激活被SlP受体的反义寡核苷酸而不是SlP 3受体的反义寡核苷酸显著抑制。在磷脂酰肌醇3-激酶抑制剂渥曼青霉素和NOS抑制剂N ω-硝基-L-精氨酸甲酯存在下，SlP刺激粘附分子表达的剂量-反应曲线向左移动。NO供体S-亚硝基-N-乙酰青霉胺抑制SIP诱导的粘附分子表达。此外，肿瘤坏死因子-α诱导的粘附分子的表达显着抑制的方式敏感的PI 3-K和NOS抑制剂的SlP。这些结果表明，SlP受体耦合到粘附分子表达的刺激和抑制途径。刺激性通路涉及核因子κ B，抑制性通路涉及磷脂酰肌醇3-激酶和NOS。(c)2005年爱思唯尔公司All rights reserved.
Sphingosine l-phosphate (SlP) stimulates expression of vascular cell adhesion molecule-1 and intercellular adhesion rnolecule-1 in human umbilical vein endothelial cells. SlP-induced actions were associated with nuclear factor kappa-B activation and inhibited by pertussis toxin as well as by antisense oligonucleotides specific to SlP receptors, especially, SlP(3). SlP also stimulated endothelial nitric oxide synthase (eNOS) and its activation was markedly inhibited by the antisense oligonucleotide for the SlP, receptor rather than that for the SlP3 receptor. The dose-response curve of SlP to stimulate adhesion molecule expression was shifted to the left in the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin and the NOS inhibitor N omega-nitro-L-arginine methyl ester. NO donor S-nitroso-N-acetylpenicillamine inhibited SIP-induced adhesion molecule expression. Moreover, tumor necrosis factor-alpha-induced adhesion molecule expression was markedly inhibited by SlP in a manner sensitive to inhibitors for PI3-K and NOS. These results suggest that SlP receptors are coupled to both stimulatory and inhibitory pathways for adhesion molecule expression. The stimulatory pathway involves nuclear factor kappa-B and inhibitory one does phosphatidylinositol 3-kinase and NOS. (c) 2005 Elsevier Inc. All rights reserved.