Sphingosine-1-phosphate prevents tumor necrosis factor-α-mediated monocyte adhesion to aortic endothelium in mice

David T. Bolick, Suseela Srinivasan, Kyu W. Kim, Melissa E. Hatley, Jeremy J. Clemens, Angela Whetzel, Nicole Ferger, Timothy L. Macdonald, Michael D. Davis, Philip S. Tsao, Kevin R. Lynch, Catherine C. Hedrick

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Objective - Endothelial activation and monocyte adhesion to endothelium are key events in inflammation. Sphingosine-1-phosphate (S1P) is a sphingolipid that binds to G protein-coupled receptors on endothelial cells (ECs). We examined the role of S1P in modulating endothelial activation and monocyte-EC interactions in vivo. Methods and Results - We injected C57BL/6J mice intravenously with tumor necrosis factor (TNF)-α in the presence and absence of the S1P1 receptor agonist SEW2871 and examined monocyte adhesion. Aortas from TNF-α-injected mice had a 4-fold increase in the number of monocytes bound, whereas aortas from TNF-α plus SEW2871-treated mice had few monocytes bound (P<0.0001). Using siRNA, we found that inhibiting the S1P1 receptor in vascular ECs blocked the ability of S1P to prevent monocyte-EC interactions in response to TNF-α. We examined signaling pathways downstream of S1P1 and found that 100 nM S1P increased phosphorylation of Akt and decreased activation of c-jun. Conclusions - Thus, we provide the first evidence that S1P signaling through the endothelial S1P1 receptor protects the vasculature against TNF-α-mediated monocyte-EC interactions in vivo.

Original languageEnglish (US)
Pages (from-to)976-981
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number5
StatePublished - May 2005
Externally publishedYes


  • Endothelium
  • Endothelium differentiation gene (Edg) receptors
  • Inflammation
  • Sphingosine-1-phosphate

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Sphingosine-1-phosphate prevents tumor necrosis factor-α-mediated monocyte adhesion to aortic endothelium in mice'. Together they form a unique fingerprint.

Cite this