title: Inhibitory effects of antithrombin on the expression of secretory group IIA phospholipase A(2) in endothelial cells.
abstract: 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.
authors.affiliation: Department of Herbal Pharmaceutical Engineering, Daegu Haany University, Gyeongsan, Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: 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
chemical_list: D000991:Antithrombins; D034741:RNA, Small Interfering; C508304:SDC4 protein, human; D053671:Syndecan-4; D014409:Tumor Necrosis Factor-alpha; D054501:Group II Phospholipases A2