Inhibitory effects of antithrombin on the expression of secretory group IIA phospholipase A(2) in endothelial cells.
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 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-α-stimulated HUVECs. TNF-α 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.
Kim
Tae Hoon
TH
Department of Herbal Pharmaceutical Engineering, Daegu Haany University, Gyeongsan, Korea.
Bae
Jong-Sup
JS
D000991:Antithrombins / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D054501:Group II Phospholipases A2 / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D034741:RNA, Small Interfering; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000991:Antithrombins; D034741:RNA, Small Interfering; C508304:SDC4 protein, human; D053671:Syndecan-4; D014409:Tumor Necrosis Factor-alpha; D054501:Group II Phospholipases A2