Inhibitory effects of antithrombin on the expression of secretory group ⅡA phospholipase A₂ in endothelial cells
2010
Kim, T.H., Daegu Haany University, Gyeongsan, Republic of Korea | Bae, J.S., Daegu Haany University, Gyeongsan, Republic of Korea
Tumor necrosis factor-α (TNF-α) mediates proinflammatory responses in primary human umbilical vein endothelial cells (HUVECs), and it upregulates the expression of secretory group ⅡA phospholipase A₂ (sPLA₂-ⅡA). sPLA₂-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 sPLA₂-ⅡA in TNF-α-stimulated HUVECs. TNF-α potently upregulated the expression of sPLA₂-ⅡA, and prior treatment of cells with AT inhibited the expression of sPLA₂-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 sPLA₂-ⅡA. These results show that AT effectively suppresses the upregulated sPLA₂-ⅡA expression, which might contribute to the cytoprotective effects of AT in the treatment of severe inflammatory diseases.
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