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Sulforaphane inhibits TNF-α-induced activation of p38 MAP kinase and VCAM-1 and MCP-1 expression in endothelial cells

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Abstract

Objective and design

To investigate the effects of sulforaphane on endothelial inflammatory gene expression in endothelial cells.

Materials and methods

Human aortic endothelial cells were used in the study.

Results

One-hour pretreatment of endothelial cells (EC) with sulforaphane (1–4 μM) suppressed TNF-α-induced MCP-1 and VCAM-1 mRNA and protein levels, but had no effect on TNF-α-induced ICAM-1 expression. Sulforaphane also inhibited TNF-α-induced activation of p38 MAP kinase, but not c-Jun-N-terminal kinase. Sulforaphane had no effect on TNF-α-induced NF-κB nuclear binding activity, IκB-α degradation or activation of NF-κB-driven transcriptional activity. Expression of dominant negative Nrf2 inhibited sulforaphane-induced antioxidant response element (ARE)-driven promoter activity, but had no effect on sulforaphane-mediated inhibition of VCAM-1 and MCP-1 expression.

Conclusion

These data suggest that sulforaphane may be useful as a therapeutic agent for the treatment of inflammatory diseases.

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Abbreviations

ARE:

Antioxidant response element

HAEC:

Human aortic endothelial cells

HMEC:

Human microvascular endothelial cells

ICAM-1:

Intercellular adhesion molecule-1

MCP-1:

Monocyte chemoattractant protein-1

Nrf2:

NF-E2-related factor-2

TNF-α:

Tumor necrosis factor-α

VCAM-1:

Vascular cell adhesion molecule-1

SFN:

Sulforaphane

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Acknowledgments

The authors wish to thank Ms Suzanne Thomas for her expert technical assistance and Dr. Dominick Sinibaldi and Dr. Danny Piper for their critical reading.

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Authors and Affiliations

  1. Discovery Research, AtheroGenics, Inc., 8995 Westside Parkway, Alpharetta, GA, 30004, USA

    Xi-Lin Chen, Geraldine Dodd & Charles Kunsch

Authors
  1. Xi-Lin Chen
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  2. Geraldine Dodd
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  3. Charles Kunsch
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Corresponding author

Correspondence to Xi-Lin Chen.

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Responsible Editor: M. J. Parnham.

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Chen, XL., Dodd, G. & Kunsch, C. Sulforaphane inhibits TNF-α-induced activation of p38 MAP kinase and VCAM-1 and MCP-1 expression in endothelial cells. Inflamm. Res. 58, 513–521 (2009). https://doi.org/10.1007/s00011-009-0017-7

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  • DOI: https://doi.org/10.1007/s00011-009-0017-7

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