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.
Original language | English |
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Pages (from-to) | 101-107 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 448 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2014 May 23 |
Bibliographical note
Funding Information:This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea Government (MSIP) ( NRF-2011-0028790 ). We thank Dr. Elaine Por for helpful comments and critical reading of this manuscript. Appendix A
All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology