NF-[kappa]B-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-[kappa]B on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of i...

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Bibliographic Details
Published in:Mediators of inflammation 2016-01, Vol.2016
Main Authors: Bao, Mei-hua, Li, Jian-Ming, Luo, Huai-qing, Tang, Liang, Lv, Qiao-li, Li, Guang- yi, Zhou, Hong-hao
Format: Article
Language:English
Subjects:
Analysis
Atherosclerosis
Cloning
Endothelium
Enzyme-linked immunosorbent assay
Inflammation
Kinases
MicroRNAs
Pathogenesis
Plasmids
Polyclonal antibodies
Proteins
Rodents
Studies
Tumor necrosis factor
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Summary: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-[kappa]B on miR-99a production. Methods and Results. ELISA showed that LPS treatment significantly promoted the secretion of inflammatory factors (TNF-[alpha], IL-6, IL-1[beta], and MCP-1). LPS treatment also inhibited miR-99a production and promoted mTOR expression and NF-[kappa]B nuclear translocation. Overexpression of miR-99a suppressed the LPS-induced TNF-[alpha], IL-6, IL-1[beta], and MCP-1 overproduction, mTOR upregulation, and NF-[kappa]B nuclear translocation. The PROMO software analysis indicated NF-[kappa]B 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-[kappa]B 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-[kappa]B on miR-99a production. Conclusion. MiR-99a inhibited the LPS-induced HUVECs inflammation via inhibition of the mTOR/NF-[kappa]B signal. NF-[kappa]B 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.
ISSN:0962-9351
1466-1861
DOI:10.1155/2016/5308170