KMID : 0624620100430090604
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BMB Reports 2010 Volume.43 No. 9 p.604 ~ p.608
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Inhibitory effects of antithrombin on the expression of secretory group IIA phospholipase A2 in endothelial cells
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Kim Tae-Hoon
Bae Jong-Sup
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Abstract
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Tumor necrosis factor-¥á (TNF-¥á) 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-¥á-stimulated HUVECs. TNF-¥á 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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KEYWORD
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Antithrombin, HUVEC, Inflammation, sPLA2-IIA, TNF-¥á
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