| | Category | BI | L05 | Proinflammatory cytokine TNF-α regulates sphingolipid |
| | signaling in Human |
| | Abstract | This experiment investigates the signaling pathways of endothelial cells, |
| | which are substituted by HUVEC (Human Umbilical Vein Endothelial Cells) |
| | in this project, which can cause arterial disease and inflammation. The |
| | experiment will use the fact that S1P (sphingosine-1-phosphate) has been |
| | shown to transactivate the TNF α (Tumor Necrosis Factor-Alpha) |
| | receptor and activate VCAM (Vascular Cell Adhesion Molecule), to find the |
| | role of S1P signaling in the induction of proinflammatory cytokine in |
| | response to TNF α activation in HUVEC and possible applications in |
| | arterial disease and cancer development cells. The experiment was |
| | performed in two steps; first, to show TNFα induces S1P receptors |
| | in the cell signaling process, and second, to prove the S1P2 receptor |
| | activates VCAM in the cell signaling process. Step one was performed by |
| | letting HUVEC treated with TNFα (no treatment, control) undertake |
| | real time PCR. The result for the first part was that S1P2 added with TNF |
| | α yielded over twice as many cells as the control. In step two, four |
| | different scenarios were presented. They are: the control, TNF α, |
| | JTE013 (the antagonist of S1P receptors), and the TNF α and JTE013 |
| | treatment. The real time PCR yielded interesting results. The VCAM |
| | expression for the TNF α treatment increased over 150 fold more |
| | than the control. The JTE013 treatment was almost the same as the |
| | control. The TNF α and JTE013 treatment increased about five fold |
| | over the control. The results showed that JTE013 could significantly inhibit |
| | TNF-α mediation of VCAM expression, suggesting that an increase |
| | of S1P2 contributes to the introduction of inflammatory cytokine VCAM in |
| | response to TNF-α. Finally, the data strongly indicates that the S1P2 |
| | pathway is an important part of the TNF-α signaling pathway and it is |
| | at least involved in the increase of the VCAM gene. The fact that TNF |
| | α activation of S1P2 expression contribute to VCAM signaling could |
| | be critical for the progression of arterial disease. Thus, this study provides |
| | new compelling evidence on the mechanism by which TNF-α gives |
| | rise to inflammation in Human arterial tissue, opening new perspectives for |
| | its pharmacological treatment. |
| | Bibliography | 1) Estrada, Rosendo. "Up-regulating Sphingosine 1-Phosphate Receptor-2 |
| | Signaling Impairs Chemotactic, Wound-healing, and Morphogenetic |
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| | http://www.jbc.org/content/283/44/30363.abstract>. 2) Wiess, Tania L. |
| | "Serial Subculture and Relative Transport of Human Endothelial Cells in |
| | Serum-free, Defined Conditions." |
| | Http://www.springerlink.com/content/5224v16n41201868/. 13 Mar. 1990. |
| | Web. 10 Nov. 2010. |
| | 3) Lee, Menq-Jer. "Vascular Endothelial Cell Adherens Junction." Cell 99 |
| | (1999): 301-12. Print. |