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Rebamipide inhibits tumor necrosis factor-α-induced interleukin-8 expression by suppressing the NF-κB signal pathway in human umbilical vein endothelial cells

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Abstract

Objective

This study was designed to identify the inhibitory effect of rebamipide on tumor necrosis factor-α (TNF-α)-induced interleukin-8 (IL-8) production and nuclear factor-κB (NF-κB) activation in human umbilical vein endothelial cells (HUVECs).

Methods

After stimulation with TNF-α, HUVECs were treated with rebamipide in a dose-dependent manner. The viability of HUVECs was assessed using methylthiazol tetrazolium assay after 24 h incubation with rebamipide. TNF-α-induced IL-8 expression was determined by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (RT–PCR). TNF-α-induced IκB-α phosphorylation and translocation of NF-κB p65 subunit into nucleus in endothelial cells were assessed using immunoblot analysis.

Results

We found that rebamipide decreased the expression of IL-8 in the dose-dependent manner under the treatment with TNF-α 10 ng/ml. TNF-α-induced degradation of IκB-α at 15 min was maximally observed and rebamipide (2 mM) inhibited TNF-α-induced phosphorylation of IκB-α in the cytoplasm of endothelial cells by western blot analysis. Rebamipide also suppressed TNF-α-stimulated NF-κB p65 nuclear translocation.

Conclusion

Rebamipide suppresses TNF-α-induced IL-8 production through (1) inhibition of IκB-α phosphorylation in the cytoplasm and (2) blockage of NF-κB p65 protein transport into the nucleus. We suggest that the anti-inflammatory effect of rebamipide is related to the down-regulation of IL-8 expression that is important in endothelial inflammation.

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Authors and Affiliations

  1. Department of Internal Medicine, Catholic University of Daegu School of Medicine, 3056-6 Daemyung 4-Dong, Namgu, Daegu, 705-718, South Korea

    Jung-Yoon Choe, Sung-Hoon Park & Seong-Kyu Kim

  2. Arthritis and Autoimmunity Research Center, Catholic University of Daegu School of Medicine, Daegu, South Korea

    Jung-Yoon Choe, Ki-Yeun Park, Seung-Jin Lee, Sung-Hoon Park & Seong-Kyu Kim

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  1. Jung-Yoon Choe
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  2. Ki-Yeun Park
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  3. Seung-Jin Lee
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  4. Sung-Hoon Park
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  5. Seong-Kyu Kim
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Correspondence to Seong-Kyu Kim.

Additional information

Responsible editor: Liwu Li.

The authors J.-Y. Choe and K.-Y. Park contributed equally to this manuscript.

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Choe, JY., Park, KY., Lee, SJ. et al. Rebamipide inhibits tumor necrosis factor-α-induced interleukin-8 expression by suppressing the NF-κB signal pathway in human umbilical vein endothelial cells. Inflamm. Res. 59, 1019–1026 (2010). https://doi.org/10.1007/s00011-010-0221-5

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  • DOI: https://doi.org/10.1007/s00011-010-0221-5

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