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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Animals, Aorta, Cell Adhesion, Cells, Cultured, Chemokines, E-Selectin, Endothelium, Vascular, Intercellular Adhesion Molecule-1, Lysophospholipids, Mice, Mice, Inbred C57BL, Monocytes, Oxadiazoles, Receptors, Lysosphingolipid, Signal Transduction, Sphingosine, Thiophenes, Tumor Necrosis Factor-alpha, Vascular Cell Adhesion Molecule-1, Vasculitis.
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Does sphingosine-1-phosphate prevent tumor necrosis factor- { alpha } -mediated monocyte adhesion to aortic endothelium in mice? Context: 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. We injected C57BL/6J mice intravenously with tumor necrosis factor (TNF)-alpha in the presence and absence of the S1P1 receptor agonist SEW2871 and examined monocyte adhesion. Aortas from TNF-alpha-injected mice had a 4-fold increase in the number of monocytes bound, whereas aortas from TNF-alpha 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-alpha. We examined signaling pathways downstream of S1P1 and found that 100 nM S1P increased phosphorylation of Akt and decreased activation of c-jun.
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Thus, we provide the first evidence that S1P signaling through the endothelial S1P1 receptor protects the vasculature against TNF-alpha-mediated monocyte-EC interactions in vivo. Final Decision: yes