Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial CellsReportar como inadecuado




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Background

Urotensin II U-II, an 11-amino acid peptide, exerts a wide range of actions in cardiovascular systems. Interleukin-8 IL-8 is secreted by endothelial cells, thereby enhancing endothelial cell survival, proliferation, and angiogenesis. However, the interrelationship between U-II and IL-8 as well as the detailed intracellular mechanism of U-II in vascular endothelial cells remain unclear. The aim of this study was to investigate the effect of U-II on IL-8 expression and to explore its intracellular mechanism in human umbilical vein endothelial cells.

Methods-Principal Findings

Primary human umbilical vein endothelial cells were used. Expression of IL-8 was determined by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and luciferase reporter assay. Western blot analyses and experiments with specific inhibitors were performed to reveal the downstream signaling pathways as concerned. U-II increased the mRNA-protein levels of IL-8 in human umbilical vein endothelial cells. The U-II effects were significantly inhibited by its receptor antagonist Orn5-URP. Western blot analyses and experiments with specific inhibitors indicated the involvement of phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase in U-II-induced IL-8 expression. Luciferase reporter assay further revealed that U-II induces the transcriptional activity of IL-8. The site-directed mutagenesis indicated that the mutation of AP-1 and NF-kB binding sites reduced U-II-increased IL-8 promoter activities. Proliferation of human umbilical vein endothelial cells induced by U-II could be inhibited significantly by IL-8 RNA interference.

Conclusion-Significance

The results show that U-II induces IL-8 expression in human umbilical vein endothelial cells via p38 mitogen-activated protein kinase and extracellular signal-regulated kinase signaling pathways and IL-8 is involved in the U-II-induced proliferation of human umbilical vein endothelial cells.



Autor: Chung-Yi Lee, Yi-Tin Tsai, Shih-Hurng Loh , Ju-Chi Liu, Tso-Hsiao Chen, Hung-Hsing Chao , Tzu-Hurng Cheng , Jin-Jer Chen

Fuente: http://plos.srce.hr/



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