Inhibitory effects of antithrombin on the expression of secretory group IIA phospholipase A2in endothelial cells

Abstract

Tumor necrosis factor-<TEX>$\alpha$</TEX> (TNF-<TEX>$\alpha$</TEX>) mediates proinflammatory responses in primary human umbilical vein endothelial cells (HUVECs), and it upregulates the expression of secretory group IIA phospholipase <TEX>$A_2$</TEX> (<TEX>$sPLA_2$</TEX>-IIA). <TEX>$sPLA_2$</TEX>-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 <TEX>$sPLA_2$</TEX>-IIA in TNF-<TEX>$\alpha$</TEX>-stimulated HUVECs. TNF-<TEX>$\alpha$</TEX> potently upregulated the expression of <TEX>$sPLA_2$</TEX>-IIA, and prior treatment of cells with AT inhibited the expression of <TEX>$sPLA_2$</TEX>-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 <TEX>$sPLA_2$</TEX>-IIA. These results show that AT effectively suppresses the upregulated <TEX>$sPLA_2$</TEX>-IIA expression, which might contribute to the cytoprotective effects of AT in the treatment of severe inflammatory diseases.