PMID- 7778058 OWN - NLM STAT- MEDLINE DCOM- 19950712 LR - 20190727 IS - 0049-3848 (Print) IS - 0049-3848 (Linking) VI - 77 IP - 5 DP - 1995 Mar 1 TI - Interferon-gamma modulates the fibrinolytic response in cultured human endothelial cells. PG - 431-40 AB - The fibrinolytic potential of the endothelial cells gives important antithrombotic properties to the vascular wall. Thrombosis is a frequent complication to atherosclerosis and other conditions where inflammatory mediators are present in the vascular wall. Inflammatory agents like lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF alpha) have been demonstrated to modulate the expression of fibrinolytic factors in cultured endothelial cells. In the present study the expression of tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (u-PA) and plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) antigen in conditioned medium from cultured human umbilical vein (HUVEC) and human saphenous vein (HSVEC) endothelial cells was investigated under basal conditions and after stimulation with LPS, TNF alpha, interferon-gamma (IFN-gamma) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNF alpha increased the expression of PAI-1, u-PA and PAI-2 in HUVEC and HSVEC, while the t-PA response differed between the two cell types. The effects of TNF alpha were modulated by IFN-gamma but not by IL-6. The increased expression of u-PA after stimulation with TNF alpha was reduced by IFN-gamma. In contrast, TNF alpha-induced expression of PAI-2 was synergistically increased by addition of IFN-gamma. These effects of IFN-gamma represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction. FAU - Arnman, V AU - Arnman V AD - Department of Surgery, Sahlgrenska University Hospital, University of Goteborg, Sweden. FAU - Stemme, S AU - Stemme S FAU - Rymo, L AU - Rymo L FAU - Risberg, B AU - Risberg B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (Plasminogen Inactivators) RN - 0 (Tumor Necrosis Factor-alpha) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.4.21.- (Plasminogen Activators) SB - IM MH - Adult MH - Cells, Cultured MH - Endothelium, Vascular/cytology/*drug effects/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Infant, Newborn MH - Interferon-gamma/*pharmacology MH - Interleukin-6/pharmacology MH - Lipopolysaccharides/pharmacology MH - Plasminogen Activators/drug effects/*metabolism MH - Plasminogen Inactivators/*metabolism MH - Tumor Necrosis Factor-alpha/pharmacology MH - Umbilical Veins/cytology EDAT- 1995/03/01 00:00 MHDA- 1995/03/01 00:01 CRDT- 1995/03/01 00:00 PHST- 1995/03/01 00:00 [pubmed] PHST- 1995/03/01 00:01 [medline] PHST- 1995/03/01 00:00 [entrez] AID - 0049-3848(95)93879-5 [pii] AID - 10.1016/0049-3848(95)93879-5 [doi] PST - ppublish SO - Thromb Res. 1995 Mar 1;77(5):431-40. doi: 10.1016/0049-3848(95)93879-5.