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Biochem Biophys Res Commun. 2014 May 23;448(1):101-7. doi: 10.1016/j.bbrc.2014.04.079. Epub 2014 Apr 21.

Functional role of NF-κB in expression of human endothelial nitric oxide synthase.

Author information

1
Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-702, South Korea.
2
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-702, South Korea.
3
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do 200-702, South Korea.
4
Department Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do 200-702, South Korea.
5
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-752, South Korea.
6
Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-702, South Korea. Electronic address: ymkim@kangwon.ac.kr.

Erratum in

  • Biochem Biophys Res Commun. 2014 Sep 12;452(1):209-10.

Abstract

The transcription factor NF-κB has an essential role in inflammation in endothelial cells. Endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) prevents vascular inflammation. However, the molecular mechanism underlying NF-κB-mediated regulation of eNOS expression has not been clearly elucidated. We here found that NF-κB-activating stimuli, such as lipopolysaccharide, tumor necrosis factor-α (TNF-α), and interleukin-1β, suppressed eNOS mRNA and protein levels by decreasing mRNA stability, without affecting promoter activity. TNF-α-mediated suppression of eNOS expression, mRNA stability, and 3'-untranslated region (3'UTR) activity were inhibited by NF-κB inhibitors and Dicer knockdown, but not by p38 MAPK and MEK inhibitors, suggesting the involvement of NF-κB-responsive miRNAs in eNOS expression. Moreover, TNF-α increased MIR155HG expression and promoter activity as well as miR-155 biogenesis, and these increases were blocked by NF-κB inhibitors. Transfection with antagomiR-155 blocked TNF-α-mediated suppression of eNOS 3'UTR activity, eNOS mRNA and protein levels, and NO and cGMP production. These data provide evidence that NF-κB is a negative regulator of eNOS expression via upregulation of miR-155 under inflammatory conditions. These results suggest that NF-κB is a potential therapeutic target for preventing vascular inflammation and endothelial dysfunction induced by suppression of miR-155-mediated eNOS expression.

KEYWORDS:

3′UTR; Endothelial nitric oxide synthase; NF-κB; TNF-α; miR-155

PMID:
24769202
DOI:
10.1016/j.bbrc.2014.04.079
[Indexed for MEDLINE]
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