NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation
Objective. The present study was performed to investigate the effects and mechanisms of miR-99a on LPS-induced endothelial cell inflammation, as well as the regulation of NF-κB on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflamm...
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2016/5308170 |
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doaj-ae70001dd7a747678db215715513d2712020-11-24T23:05:06ZengHindawi LimitedMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/53081705308170NF-κB-Regulated miR-99a Modulates Endothelial Cell InflammationMei-hua Bao0Jian-Ming Li1Huai-qing Luo2Liang Tang3Qiao-li Lv4Guang-yi Li5Hong-hao Zhou6Department of Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha 410219, ChinaDepartment of Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha 410219, ChinaDepartment of Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha 410219, ChinaDepartment of Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha 410219, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha 410219, ChinaDepartment of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, ChinaObjective. The present study was performed to investigate the effects and mechanisms of miR-99a on LPS-induced endothelial cell inflammation, as well as the regulation of NF-κB on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflammatory factors (TNF-α, IL-6, IL-1β, and MCP-1). LPS treatment also inhibited miR-99a production and promoted mTOR expression and NF-κB nuclear translocation. Overexpression of miR-99a suppressed the LPS-induced TNF-α, IL-6, IL-1β, and MCP-1 overproduction, mTOR upregulation, and NF-κB nuclear translocation. The PROMO software analysis indicated NF-κB binding site in the −1643 to −1652 region of miR-99a promoter. Dual luciferase reporter analysis, electrophoretic mobility shift assays (EMSA), and chromosome immunoprecipitation (ChIP) assays demonstrated that NF-κB promoted the transcription of miR-99a by binding to the −1643 to −1652 region of miR-99a promoter. Further studies on HUVECs verified the regulatory effects of NF-κB on miR-99a production. Conclusion. MiR-99a inhibited the LPS-induced HUVECs inflammation via inhibition of the mTOR/NF-κB signal. NF-κB promoted miR-99a production by binding to the −1643 to −1652 region of miR-99a promoter. Considering the importance of endothelial inflammation on cardiovascular diseases, such as atherosclerosis, our results may provide a new insight into the pathogenesis and therapy of atherosclerosis.http://dx.doi.org/10.1155/2016/5308170 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mei-hua Bao Jian-Ming Li Huai-qing Luo Liang Tang Qiao-li Lv Guang-yi Li Hong-hao Zhou |
spellingShingle |
Mei-hua Bao Jian-Ming Li Huai-qing Luo Liang Tang Qiao-li Lv Guang-yi Li Hong-hao Zhou NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation Mediators of Inflammation |
author_facet |
Mei-hua Bao Jian-Ming Li Huai-qing Luo Liang Tang Qiao-li Lv Guang-yi Li Hong-hao Zhou |
author_sort |
Mei-hua Bao |
title |
NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation |
title_short |
NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation |
title_full |
NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation |
title_fullStr |
NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation |
title_full_unstemmed |
NF-κB-Regulated miR-99a Modulates Endothelial Cell Inflammation |
title_sort |
nf-κb-regulated mir-99a modulates endothelial cell inflammation |
publisher |
Hindawi Limited |
series |
Mediators of Inflammation |
issn |
0962-9351 1466-1861 |
publishDate |
2016-01-01 |
description |
Objective. The present study was performed to investigate the effects and mechanisms of miR-99a on LPS-induced endothelial cell inflammation, as well as the regulation of NF-κB on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflammatory factors (TNF-α, IL-6, IL-1β, and MCP-1). LPS treatment also inhibited miR-99a production and promoted mTOR expression and NF-κB nuclear translocation. Overexpression of miR-99a suppressed the LPS-induced TNF-α, IL-6, IL-1β, and MCP-1 overproduction, mTOR upregulation, and NF-κB nuclear translocation. The PROMO software analysis indicated NF-κB binding site in the −1643 to −1652 region of miR-99a promoter. Dual luciferase reporter analysis, electrophoretic mobility shift assays (EMSA), and chromosome immunoprecipitation (ChIP) assays demonstrated that NF-κB promoted the transcription of miR-99a by binding to the −1643 to −1652 region of miR-99a promoter. Further studies on HUVECs verified the regulatory effects of NF-κB on miR-99a production. Conclusion. MiR-99a inhibited the LPS-induced HUVECs inflammation via inhibition of the mTOR/NF-κB signal. NF-κB promoted miR-99a production by binding to the −1643 to −1652 region of miR-99a promoter. Considering the importance of endothelial inflammation on cardiovascular diseases, such as atherosclerosis, our results may provide a new insight into the pathogenesis and therapy of atherosclerosis. |
url |
http://dx.doi.org/10.1155/2016/5308170 |
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