PMID- 20846492 OWN - NLM STAT- MEDLINE DCOM- 20101228 LR - 20100917 IS - 1976-670X (Electronic) IS - 1976-6696 (Linking) VI - 43 IP - 9 DP - 2010 Sep TI - Inhibitory effects of antithrombin on the expression of secretory group IIA phospholipase A(2) in endothelial cells. PG - 604-8 LID - 10.5483/BMBRep.2010.43.9.604 [doi] AB - 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. FAU - Kim, Tae Hoon AU - Kim TH AD - Department of Herbal Pharmaceutical Engineering, Daegu Haany University, Gyeongsan, Korea. FAU - Bae, Jong-Sup AU - Bae JS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Korea (South) TA - BMB Rep JT - BMB reports JID - 101465334 RN - 0 (Antithrombins) RN - 0 (RNA, Small Interfering) RN - 0 (SDC4 protein, human) RN - 0 (Syndecan-4) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.1.1.4 (Group II Phospholipases A2) SB - IM MH - Antithrombins/*pharmacology MH - Blotting, Western MH - Cells, Cultured MH - Endothelial Cells/*drug effects/*enzymology MH - Enzyme Activation/drug effects/genetics MH - Enzyme-Linked Immunosorbent Assay MH - Group II Phospholipases A2/*metabolism MH - Humans MH - Inhibitory Concentration 50 MH - RNA, Small Interfering MH - Syndecan-4/genetics/metabolism MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 2010/09/18 06:00 MHDA- 2010/12/29 06:00 CRDT- 2010/09/18 06:00 PHST- 2010/09/18 06:00 [entrez] PHST- 2010/09/18 06:00 [pubmed] PHST- 2010/12/29 06:00 [medline] AID - 10.5483/BMBRep.2010.43.9.604 [doi] PST - ppublish SO - BMB Rep. 2010 Sep;43(9):604-8. doi: 10.5483/BMBRep.2010.43.9.604.