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Inhibitory effects of epi-sesamin on endothelial protein C receptor shedding in vitro and in vivo

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Abstract

Objective and design

Endothelial protein C receptor (EPCR) plays a pivotal role in augmenting Protein C activation by the thrombin–thrombomodulin complex. The activity of EPCR is markedly changed by ectodomain cleavage and release as the soluble protein (sEPCR). The EPCR shedding is mediated by the tumor necrosis factor-α converting enzyme (TACE). Epi-sesamin (ESM), from the roots of Asarum siebodlii, is known to exhibit anti-allergic and anti-fungal activities. However, little is known about the effects of ESM on EPCR shedding.

Methods

We investigated this issue by monitoring the effects of ESM on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and cecal ligation and puncture (CLP)-mediated EPCR shedding.

Results

Data showed that ESM induced potent inhibition of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding, likely through suppression of TACE expression. In addition, treatment with ESM resulted in a reduction of PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK).

Conclusions

Given these results, ESM should be viewed as a candidate therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of EPCR shedding.

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Acknowledgments

This study was supported by the National Research Foundation of Korea (NRF) funded by the Korea government [MEST] (Grant No. 2012-0009400) and by the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. A111305).

Conflict of interest

The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan, 712-715, Republic of Korea

    Sae-Kwang Ku

  2. College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea

    Wonhwa Lee, Hayoung Yoo & Jong-Sup Bae

  3. Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, 702-701, Republic of Korea

    Wonhwa Lee

  4. Department of Oriental Medicinal Materials and Processing, College of Life Science, Kyung Hee University, Yongin, 446-701, Republic of Korea

    Chang-Kyun Han

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  1. Sae-Kwang Ku
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  2. Wonhwa Lee
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Correspondence to Jong-Sup Bae.

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Responsible Editor: Liwu Li.

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Ku, SK., Lee, W., Yoo, H. et al. Inhibitory effects of epi-sesamin on endothelial protein C receptor shedding in vitro and in vivo. Inflamm. Res. 62, 895–902 (2013). https://doi.org/10.1007/s00011-013-0648-6

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  • DOI: https://doi.org/10.1007/s00011-013-0648-6

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