Sphingosine-1-phosphate receptor-2 mediated NFκB activation contributes to tumor necrosis factor-α induced VCAM-1 and ICAM-1 expression in endothelial cells.
Sphingosine-1-phosphate receptor-2 mediated NFκB activation contributes to tumor necrosis factor-α induced VCAM-1 and ICAM-1 expression in endothelial cells.
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DOI：
10.1016/j.prostaglandins.2013.06.001
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发表时间：
2013-10
影响因子：
2.9
通讯作者：
Lee MJ
中科院分区：
文献类型：
--
作者：
Zhang W;An J;Jawadi H;Siow DL;Lee JF;Zhao J;Gartung A;Maddipati KR;Honn KV;Wattenberg BW;Lee MJ
Sphingosine-1-phosphate (S1P) regulates a wide array of biological functions in endothelial cells. We previously showed that S1P receptor subtype 2 (S1P2) is significantly up-regulated in the atherosclerotic endothelium (J. Biol. Chem. 283:30363, 2008). In this study, we investigated the roles of S1P2-mediated signaling in the proinflammatory responses of endothelial cells. Treatment with tumor necrosis factor-α (TNFα), a proinflammatory cytokine, increased the expression of S1P2 receptors in endothelial cells. TNFα treatment also enhanced sphingosine kinase 1 expression and increased S1P production. Pharmacological inhibition or knockdown of S1P2 receptors completely abrogated the TNFα-induced VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) expression in endothelial cells. In contrast, pharmacological inhibition or knockdown of other S1P receptor subtypes had no effect on the TNFα-stimulated ICAM-1 and VCAM-1 expression. Moreover, ectopic expression of S1P2 receptors increased VCAM-1 and ICAM-1 expression in endothelial cells in response to S1P stimulation. Mechanistically, we show that antagonizing S1P2 signaling markedly inhibited the TNFα-stimulated NFκB activation. Utilizing the NFκB reporter luciferase assay, the S1P/S1P2 signaling was shown to stimulate NFκB activation. Moreover, the S1P/S1P2-stimulated VCAM-1/ICAM-1 expression was completely abolished by the pharmacological inhibitor of NFκB. Collectively, our data suggest that TNFα treatment activates autocrine S1P/S1P2 signaling, which subsequently activates NFκB and leads to the proinflammatory responses in endothelial cells.
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影响因子：
5.2
作者：
Hsu A;Zhang W;Lee JF;An J;Ekambaram P;Liu J;Honn KV;Klinge CM;Lee MJ
通讯作者：
Lee MJ
DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hait NC;Allegood J;Maceyka M;Strub GM;Harikumar KB;Singh SK;Luo C;Marmorstein R;Kordula T;Milstien S;Spiegel S
通讯作者：
Spiegel S
DOI：
10.1152/ajpheart.00097.2008
发表时间：
2009-01-01
影响因子：
4.8
作者：
Lee, Jen-Fu;Gordon, Sharon;Lee, Menq-Jer
通讯作者：
Lee, Menq-Jer
影响因子：
4.4
作者：
Lai, Wen-Qi;Irwan, Anastasia Windy;Leung, Bernard P.
通讯作者：
Leung, Bernard P.
影响因子：
56.9
作者：
Lee, MJ;Van Brocklyn, JR;Hla, T
通讯作者：
Hla, T