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Salusin-β, but Not Salusin-α, Promotes Human Umbilical Vein Endothelial Cell Inflammation via the p38 MAPK/JNK-NF-κB Pathway

OBJECTIVE: Recently, salusin-β has been reported to have pro-atherosclerotic effects, but salusin-α has anti-atherosclerotic effects. Our previous study has shown that salusin-β but not salusin-α promotes vascular inflammation in apoE-deficient mice. However, the underlying mechanism remains unknown...

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Autores principales: Zhou, Cheng-Hua, Pan, Jin, Huang, He, Zhu, Yangzi, Zhang, Mingxing, Liu, Lian, Wu, Yuqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161457/
https://www.ncbi.nlm.nih.gov/pubmed/25210730
http://dx.doi.org/10.1371/journal.pone.0107555
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author Zhou, Cheng-Hua
Pan, Jin
Huang, He
Zhu, Yangzi
Zhang, Mingxing
Liu, Lian
Wu, Yuqing
author_facet Zhou, Cheng-Hua
Pan, Jin
Huang, He
Zhu, Yangzi
Zhang, Mingxing
Liu, Lian
Wu, Yuqing
author_sort Zhou, Cheng-Hua
collection PubMed
description OBJECTIVE: Recently, salusin-β has been reported to have pro-atherosclerotic effects, but salusin-α has anti-atherosclerotic effects. Our previous study has shown that salusin-β but not salusin-α promotes vascular inflammation in apoE-deficient mice. However, the underlying mechanism remains unknown. In this study, we observed the effect of salusins on inflammatory responses and the MAPK-NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: HUVECs were incubated with different concentrations of salusin-α and salusin-β. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined using enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were quantified using quantitative real-time polymerase chain reaction (PCR). The protein expressions of VCAM-1, MCP-1, I-κBα, NF-κB, p-JNK and p-p38 MAPK were measured using western blotting analysis. Our results showed that in HUVECs, salusin-β could up-regulate the levels of IL-6, TNF-α, VCAM-1 and MCP-1, promote I-κBα degradation and NF-κB activation, and increase the phosphorylation of JNK and p38 MAPK. These effects could be inhibited by p38 MAPK inhibitor SB203580 and/or JNK inhibitor SP600125. In contrast, salusin-α could selectively decrease VCAM-1 protein, but did not show any effect on the expressions of VCAM-1 mRNA, TNF-α, IL-6, MCP-1, I-κBα, NF-κB, p-JNK or p-p38 MAPK. CONCLUSION: Salusin-β was able to promote inflammatory responses in HUVECs via the p38 MAPK-NF-κB and JNK-NF-κB pathways. In contrast, salusin-α failed to show any significant effects on the inflammatory responses in HUVECs. These results provide further insight into the mechanisms behind salusins in vascular inflammation and offer a potential target for the prevention and treatment of atherosclerosis.
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spelling pubmed-41614572014-09-17 Salusin-β, but Not Salusin-α, Promotes Human Umbilical Vein Endothelial Cell Inflammation via the p38 MAPK/JNK-NF-κB Pathway Zhou, Cheng-Hua Pan, Jin Huang, He Zhu, Yangzi Zhang, Mingxing Liu, Lian Wu, Yuqing PLoS One Research Article OBJECTIVE: Recently, salusin-β has been reported to have pro-atherosclerotic effects, but salusin-α has anti-atherosclerotic effects. Our previous study has shown that salusin-β but not salusin-α promotes vascular inflammation in apoE-deficient mice. However, the underlying mechanism remains unknown. In this study, we observed the effect of salusins on inflammatory responses and the MAPK-NF-κB signaling pathway in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: HUVECs were incubated with different concentrations of salusin-α and salusin-β. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined using enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were quantified using quantitative real-time polymerase chain reaction (PCR). The protein expressions of VCAM-1, MCP-1, I-κBα, NF-κB, p-JNK and p-p38 MAPK were measured using western blotting analysis. Our results showed that in HUVECs, salusin-β could up-regulate the levels of IL-6, TNF-α, VCAM-1 and MCP-1, promote I-κBα degradation and NF-κB activation, and increase the phosphorylation of JNK and p38 MAPK. These effects could be inhibited by p38 MAPK inhibitor SB203580 and/or JNK inhibitor SP600125. In contrast, salusin-α could selectively decrease VCAM-1 protein, but did not show any effect on the expressions of VCAM-1 mRNA, TNF-α, IL-6, MCP-1, I-κBα, NF-κB, p-JNK or p-p38 MAPK. CONCLUSION: Salusin-β was able to promote inflammatory responses in HUVECs via the p38 MAPK-NF-κB and JNK-NF-κB pathways. In contrast, salusin-α failed to show any significant effects on the inflammatory responses in HUVECs. These results provide further insight into the mechanisms behind salusins in vascular inflammation and offer a potential target for the prevention and treatment of atherosclerosis. Public Library of Science 2014-09-11 /pmc/articles/PMC4161457/ /pubmed/25210730 http://dx.doi.org/10.1371/journal.pone.0107555 Text en © 2014 Zhou 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
Zhou, Cheng-Hua
Pan, Jin
Huang, He
Zhu, Yangzi
Zhang, Mingxing
Liu, Lian
Wu, Yuqing
Salusin-β, but Not Salusin-α, Promotes Human Umbilical Vein Endothelial Cell Inflammation via the p38 MAPK/JNK-NF-κB Pathway
title Salusin-β, but Not Salusin-α, Promotes Human Umbilical Vein Endothelial Cell Inflammation via the p38 MAPK/JNK-NF-κB Pathway
title_full Salusin-β, but Not Salusin-α, Promotes Human Umbilical Vein Endothelial Cell Inflammation via the p38 MAPK/JNK-NF-κB Pathway
title_fullStr Salusin-β, but Not Salusin-α, Promotes Human Umbilical Vein Endothelial Cell Inflammation via the p38 MAPK/JNK-NF-κB Pathway
title_full_unstemmed Salusin-β, but Not Salusin-α, Promotes Human Umbilical Vein Endothelial Cell Inflammation via the p38 MAPK/JNK-NF-κB Pathway
title_short Salusin-β, but Not Salusin-α, Promotes Human Umbilical Vein Endothelial Cell Inflammation via the p38 MAPK/JNK-NF-κB Pathway
title_sort salusin-β, but not salusin-α, promotes human umbilical vein endothelial cell inflammation via the p38 mapk/jnk-nf-κb pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161457/
https://www.ncbi.nlm.nih.gov/pubmed/25210730
http://dx.doi.org/10.1371/journal.pone.0107555
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