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Piceatannol inhibits phorbol ester-induced expression of COX-2 and iNOS in HR-1 hairless mouse skin by blocking the activation of NF-κB and AP-1

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Abstract

Objectives

The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory activity of piceatannol (trans-3,4,3′,5′-tetrahydroxystilbene) in mouse skin in vivo.

Methods

Female HR-1 hairless mice were topically treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) with or without piceatannol pretreatment. Epidermal protein expression was assessed by Western blot analysis. The cyclooxygenase-2 (COX-2) expression was detected by immunohistochemistry. The DNA binding of nuclear factor-kappaB (NF-κB) and activator protein-1 (AP-1) was examined by the electrophoretic mobility gel shift assay. The catalytic activity of IκBα kinase-β (IKKβ) was measured by in vitro kinase assay.

Results

Pretreatment with piceatannol attenuated TPA-induced expression of COX-2 and inducible nitric oxide synthase (iNOS) in mouse skin. Piceatannol diminished nuclear translocation and the DNA binding of NF-κB through the blockade of phosphorylation and subsequent degradation of IκBα. Piceatannol attenuated the catalytic activity of IKKβ and inhibited the phosphorylation of mitogen-activated protein (MAP) kinases in TPA-treated mouse skin. In addition, piceatannol decreased TPA-induced expression of c-Fos and the DNA binding of AP-1.

Conclusion

Piceatannol inhibits TPA-induced COX-2 and iNOS expression by blocking the activation of NF-κB and AP-1 via suppression of the IKKβ activity and phosphorylation of MAP kinases, which provides a mechanistic basis of its anti-inflammatory effects in mouse skin.

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Acknowledgments

This work has been supported by the Settlement Research Grant-2012-0195 of Keimyung University allocated to Joydeb Kumar Kundu.

Conflict of interest

Authors declare that no conflict of interest exists.

Author information

Authors and Affiliations

  1. Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea

    Lijia Liu & Young-Joon Surh

  2. Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, People’s Republic of China

    Lijia Liu & Jianchun Li

  3. College of Pharmacy, Keimyung University, Daegu, 704-701, South Korea

    Joydeb Kumar Kundu

  4. Cancer Research Institute, Seoul National University, Seoul, 110-799, South Korea

    Young-Joon Surh

Authors
  1. Lijia Liu
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  2. Jianchun Li
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Corresponding author

Correspondence to Joydeb Kumar Kundu.

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Responsible Editor: Liwu Li.

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Liu, L., Li, J., Kundu, J.K. et al. Piceatannol inhibits phorbol ester-induced expression of COX-2 and iNOS in HR-1 hairless mouse skin by blocking the activation of NF-κB and AP-1. Inflamm. Res. 63, 1013–1021 (2014). https://doi.org/10.1007/s00011-014-0777-6

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  • DOI: https://doi.org/10.1007/s00011-014-0777-6

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