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Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial Cells
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931834/ https://www.ncbi.nlm.nih.gov/pubmed/24587311 http://dx.doi.org/10.1371/journal.pone.0090278 |
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author | Lee, Chung-Yi Tsai, Yi-Tin Loh, Shih-Hurng Liu, Ju-Chi Chen, Tso-Hsiao Chao, Hung-Hsing Cheng, Tzu-Hurng Chen, Jin-Jer |
author_facet | Lee, Chung-Yi Tsai, Yi-Tin Loh, Shih-Hurng Liu, Ju-Chi Chen, Tso-Hsiao Chao, Hung-Hsing Cheng, Tzu-Hurng Chen, Jin-Jer |
author_sort | Lee, Chung-Yi |
collection | PubMed |
description | 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 [Orn(5)]-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. |
format | Online Article Text |
id | pubmed-3931834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39318342014-02-25 Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial Cells Lee, Chung-Yi Tsai, Yi-Tin Loh, Shih-Hurng Liu, Ju-Chi Chen, Tso-Hsiao Chao, Hung-Hsing Cheng, Tzu-Hurng Chen, Jin-Jer PLoS One Research Article 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 [Orn(5)]-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. Public Library of Science 2014-02-21 /pmc/articles/PMC3931834/ /pubmed/24587311 http://dx.doi.org/10.1371/journal.pone.0090278 Text en © 2014 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lee, Chung-Yi Tsai, Yi-Tin Loh, Shih-Hurng Liu, Ju-Chi Chen, Tso-Hsiao Chao, Hung-Hsing Cheng, Tzu-Hurng Chen, Jin-Jer Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial Cells |
title | Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial Cells |
title_full | Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial Cells |
title_fullStr | Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial Cells |
title_full_unstemmed | Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial Cells |
title_short | Urotensin II Induces Interleukin 8 Expression in Human Umbilical Vein Endothelial Cells |
title_sort | urotensin ii induces interleukin 8 expression in human umbilical vein endothelial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931834/ https://www.ncbi.nlm.nih.gov/pubmed/24587311 http://dx.doi.org/10.1371/journal.pone.0090278 |
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