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http://dx.doi.org/10.5483/BMBRep.2010.43.9.604

Inhibitory effects of antithrombin on the expression of secretory group IIA phospholipase A2 in endothelial cells  

Kim, Tae-Hoon (Department of Herbal Medicinal Pharmacology, College of Herbal Bio-Industry, Daegu Haany University)
Bae, Jong-Sup (Department of Herbal Pharmaceutical Engineering, College of Herbal Bio-Industry, Daegu Haany University)
Publication Information
BMB Reports / v.43, no.9, 2010 , pp. 604-608 More about this Journal
Abstract
Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) 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-$\alpha$-stimulated HUVECs. TNF-$\alpha$ 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.
Keywords
Antithrombin; HUVEC; Inflammation; $sPLA_2$-IIA; TNF-$\alpha$;
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1 Nakano, T., Ohara, O., Teraoka, H. and Arita, H. (1990) Glucocorticoids suppress group II phospholipase A2 production by blocking mRNA synthesis and post-transcriptional expression. J. Biol. Chem. 265, 12745-12748.
2 Pruzanski, W. and Vadas, P. (1991) Phospholipase A2--a mediator between proximal and distal effectors of inflammation. Immunol. Today 12, 143-146.
3 Bradley, J. D., Dmitrienko, A. A., Kivitz, A. J., Gluck, O. S., Weaver, A. L., Wiesenhutter, C., Myers, S. L. and Sides, G. D. (2005) A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis. J. Rheumatol. 32, 417-423.   DOI
4 Zeiher, B. G., Steingrub, J., Laterre, P. F., Dmitrienko, A., Fukiishi, Y. and Abraham, E. (2005) LY315920NA/S-5920, a selective inhibitor of group IIA secretory phospholipase A2, fails to improve clinical outcome for patients with severe sepsis. Crit. Care Med. 33, 1741-1748.   DOI   ScienceOn
5 Yamauchi, T., Umeda, F., Inoguchi, T. and Nawata, H. (1989) Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells. Biochem. Biophys Res. Commun 163, 1404-1411.   DOI   ScienceOn
6 Hoffmann, J. N., Vollmar, B., Romisch, J., Inthorn, D., Schildberg, F. W. and Menger, M. D. (2002) Antithrombin effects on endotoxin-induced microcirculatory disorders are mediated mainly by its interaction with microvascular endothelium. Crit. Care Med. 30, 218-225.   DOI   ScienceOn
7 Kaneider, N. C., Reinisch, C. M., Dunzendorfer, S., Romisch, J. and Wiedermann, C. J. (2002) Syndecan-4 mediates antithrombin-induced chemotaxis of human peripheral blood lymphocytes and monocytes. J. Cell Sci. 115, 227-236.
8 Menschikowski, M., Hagelgans, A., Hempel, U., Lattke, P., Ismailov, I. and Siegert, G. (2008) On interaction of activated protein C with human aortic smooth muscle cells attenuating the secretory group IIA phospholipase A2 expression. Thromb. Res. 122, 69-76.   DOI   ScienceOn
9 Bae, J. S. and Rezaie, A. R. (2010) Thrombin and activated protein C inhibit the expression of secretory group IIA phospholipase A(2) in the TNF-alpha-activated endothelial cells by EPCR and PAR-1 dependent mechanisms. Thromb. Res. 125, e9-e15.   DOI   ScienceOn
10 Sonoki, K., Iwase, M., Sasaki, N., Ohdo, S., Higuchi, S., Takata, Y. and Iida, M. (2008) Secretory PLA2 inhibitor indoxam suppresses LDL modification and associated inflammatory responses in TNFalpha-stimulated human endothelial cells. Br. J. Pharmacol. 153, 1399-1408.   DOI   ScienceOn
11 Hayashi, H., Tsuchiya, Y., Nakayama, K., Satoh, T. and Nishida, E. (2008) Down-regulation of the PI3-kinase/Akt pathway by ERK MAP kinase in growth factor signaling. Genes Cells 13, 941-947.   DOI   ScienceOn
12 Yao, R. and Cooper, G. M. (1995) Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267, 2003-2006.   DOI
13 Crowl, R. M., Stoller, T. J., Conroy, R. R. and Stoner, C. R. (1991) Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response. J. Biol. Chem. 266, 2647-2651.
14 Minshall, C., Arkins, S., Freund, G. G. and Kelley, K. W. (1996) Requirement for phosphatidylinositol 3'-kinase to protect hemopoietic progenitors against apoptosis depends upon the extracellular survival factor. J. Immunol. 156, 939-947.
15 Ahmed, N. N., Grimes, H. L., Bellacosa, A., Chan, T. O. and Tsichlis, P. N. (1997) Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc. Natl. Acad. Sci. U.S.A. 94, 3627-3632.   DOI
16 Bae, J. S., Kim, Y. U., Park, M. K. and Rezaie, A. R. (2009) Concentration dependent dual effect of thrombin in endothelial cells via Par-1 and Pi3 Kinase. J. Cell Physiol. 219, 744-751.   DOI   ScienceOn
17 Oka, S. and Arita, H. (1991) Inflammatory factors stimulate expression of group II phospholipase A2 in rat cultured astrocytes. Two distinct pathways of the gene expression. J. Biol. Chem. 266, 9956-9960.
18 Marcum, J. A. and Rosenberg, R. D. (1984) Anticoagulantly active heparin-like molecules from vascular tissue. Biochemistry 23, 1730-1737.   DOI   ScienceOn
19 Kaneider, N. C., Egger, P., Dunzendorfer, S. and Wiedermann, C. J. (2001) Syndecan-4 as antithrombin receptor of human neutrophils. Biochem. Biophys. Res. Commun. 287, 42-46.   DOI   ScienceOn
20 Parrillo, J. E. (1993) Pathogenetic mechanisms of septic shock. N. Engl. J. Med. 328, 1471-1477.   DOI   ScienceOn
21 Bass, M. D. and Humphries, M. J. (2002) Cytoplasmic interactions of syndecan-4 orchestrate adhesion receptor and growth factor receptor signalling. Biochem. J. 368, 1-15.   DOI   ScienceOn
22 Menschikowski, M., Hagelgans, A. and Siegert, G. (2006) Secretory phospholipase A2 of group IIA: is it an offensive or a defensive player during atherosclerosis and other inflammatory diseases? Prostaglandins. Other. Lipid. Mediat. 79, 1-33.   DOI   ScienceOn
23 Delehedde, M., Lyon, M., Sergeant, N., Rahmoune, H. and Fernig, D. G. (2001) Proteoglycans: pericellular and cell surface multireceptors that integrate external stimuli in the mammary gland. J. Mammary. Gland. Biol. Neoplasia. 6, 253-273.   DOI   ScienceOn
24 Kaneider, N. C., Forster, E., Mosheimer, B., Sturn, D. H. and Wiedermann, C. J. (2003) Syndecan-4-dependent signaling in the inhibition of endotoxin-induced endothelial adherence of neutrophils by antithrombin. Thromb. Haemost. 90, 1150-1157.
25 Bae, J. S. and Rezaie, A. R. (2009) Mutagenesis studies toward understanding the intracellular signaling mechanism of antithrombin. J. Thromb. Haemost. 7, 803-810.   DOI   ScienceOn
26 Kudo, I. and Murakami, M. (2002) Phospholipase A2 enzymes. Prostaglandins. Other. Lipid. Mediat. 68-69, 3-58.   DOI   ScienceOn