Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells

  • Authors:
    • Po-Min Yang
    • Huang-Zhi Chen
    • Yu-Ting Huang
    • Chia-Wen Hsieh
    • Being-Sun Wung
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  • Published online on: April 20, 2017     https://doi.org/10.3892/ijmm.2017.2960
  • Pages: 1533-1540
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Abstract

The endothelial expression of cell adhesion molecules plays a leading role in atherosclerosis. Lycopene, a carotenoid with 11 conjugated double bonds, has been shown to have anti-inflammatory properties. In the present study, we demonstrate a putative mechanism for the anti-inflammatory effects of lycopene. We demonstrate that lycopene inhibits the adhesion of tumor necrosis factor α (TNFα)-stimulated monocytes to endothelial cells and suppresses the expression of intercellular cell adhesion molecule-1 (ICAM-1) at the transcriptional level. Moreover, lycopene was found to exert its inhibitory effects by blocking the degradation of the inhibitory protein, IκBα, following 6 h of pre-treatment. In TNFα-stimulated endothelial cells, nuclear factor-κB (NF-κB) nuclear translocation and transcriptional activity were abolished by up to 12 h of lycopene pre-treatment. We also found that lycopene increased the intracellular glutathione (GSH) level and glutamate-cysteine ligase expression. Subsequently, lycopene induced nuclear factor-erythroid 2 related factor 2 (Nrf2) activation, leading to the increased expression of downstream of heme oxygenase-1 (HO-1). The use of siRNA targeting HO-1 blocked the inhibitory effects of lycopene on IκB degradation and ICAM-1 expression. The inhibitory effects of lycopene thus appear to be mediated through its induction of Nrf2-mediated HO-1 expression. Therefore, the findings of the present study indicate that lycopene suppresses the activation of TNFα-induced signaling pathways through the upregulation of Nrf2-mediated HO-1 expression.
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June-2017
Volume 39 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yang P, Chen H, Huang Y, Hsieh C and Wung B: Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells. Int J Mol Med 39: 1533-1540, 2017.
APA
Yang, P., Chen, H., Huang, Y., Hsieh, C., & Wung, B. (2017). Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells. International Journal of Molecular Medicine, 39, 1533-1540. https://doi.org/10.3892/ijmm.2017.2960
MLA
Yang, P., Chen, H., Huang, Y., Hsieh, C., Wung, B."Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells". International Journal of Molecular Medicine 39.6 (2017): 1533-1540.
Chicago
Yang, P., Chen, H., Huang, Y., Hsieh, C., Wung, B."Lycopene inhibits NF-κB activation and adhesion molecule expression through Nrf2-mediated heme oxygenase-1 in endothelial cells". International Journal of Molecular Medicine 39, no. 6 (2017): 1533-1540. https://doi.org/10.3892/ijmm.2017.2960