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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Inhibitory effects of antithrombin on the expression of secretory group IIA phospholipase A2 in endothelial cells

  • Kim, Tae-Hoon (Department of Herbal Medicinal Pharmacology, College of Herbal Bio-Industry, Daegu Haany University) ;
  • Bae, Jong-Sup (Department of Herbal Pharmaceutical Engineering, College of Herbal Bio-Industry, Daegu Haany University)
  • Received : 2010.05.10
  • Accepted : 2010.06.17
  • Published : 2010.09.30
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Abstract

Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) mediates proinflammatory responses in primary human umbilical vein endothelial cells (HUVECs), and it upregulates the expression of secretory group IIA phospholipase $A_2$ ($sPLA_2$-IIA). $sPLA_2$-IIA plays a pivotal role in inflammation, and antithrombin (AT) possesses properties that are beneficial to endothelial cells. Therefore, we investigated the effects of AT on the expression of $sPLA_2$-IIA in TNF-$\alpha$-stimulated HUVECs. TNF-$\alpha$ potently upregulated the expression of $sPLA_2$-IIA, and prior treatment of cells with AT inhibited the expression of $sPLA_2$-IIA in HUVECs. Also, antibodies or siRNA for syndecan-4 blocked the protective effect of AT. Furthermore, PI3-kinase and the AKT pathway are significantly involved in the AT-mediated inhibition of the expression of $sPLA_2$-IIA. These results show that AT effectively suppresses the upregulated $sPLA_2$-IIA expression, which might contribute to the cytoprotective effects of AT in the treatment of severe inflammatory diseases.

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References

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