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Interferon-γ modulates the fibrinolytic response in cultured human endothelial cells
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...
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| Published in: | Thrombosis research 1995-03, Vol.77 (5), p.431-440 |
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| Main Authors: | , , , |
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| Language: | English |
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| container_end_page | 440 |
| container_issue | 5 |
| container_start_page | 431 |
| container_title | Thrombosis research |
| container_volume | 77 |
| creator | Arnman, Veronika Stemme, Sten Rymo, Lars Risberg, Bo |
| description | 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-α (TNFα) 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, TNFα, interferon-γ (IFN-γ) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNFα 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 TNFα were modulated by IFN-γ but not by IL-6. The increased expression of u-PA after stimulation with TNFα was reduced by IFN-γ. In contrast, TNFα-induced expression of PAI-2 was synergistically increased by addition of IFN-γ. These effects of IFN-γ represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction. |
| doi_str_mv | 10.1016/0049-3848(95)93879-5 |
| format | article |
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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-α (TNFα) 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, TNFα, interferon-γ (IFN-γ) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNFα 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 TNFα were modulated by IFN-γ but not by IL-6. The increased expression of u-PA after stimulation with TNFα was reduced by IFN-γ. In contrast, TNFα-induced expression of PAI-2 was synergistically increased by addition of IFN-γ. These effects of IFN-γ represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction.</description><identifier>ISSN: 0049-3848</identifier><identifier>EISSN: 1879-2472</identifier><identifier>DOI: 10.1016/0049-3848(95)93879-5</identifier><identifier>PMID: 7778058</identifier><identifier>CODEN: THBRAA</identifier><language>eng</language><publisher>New York, NY: Elsevier Ltd</publisher><subject>Adult ; Biological and medical sciences ; Blood coagulation. Blood cells ; Cells, Cultured ; endothelial cells ; Endothelium, Vascular - cytology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Enzyme-Linked Immunosorbent Assay ; fibrinolysis ; Fundamental and applied biological sciences. Psychology ; General aspects, investigation methods, hemostasis, fibrinolysis ; Humans ; Infant, Newborn ; inflammatory cytokines ; Interferon-gamma - pharmacology ; Interleukin-6 - pharmacology ; Lipopolysaccharides - pharmacology ; Molecular and cellular biology ; plasminogen activator ; plasminogen activator inhibitor ; Plasminogen Activators - drug effects ; Plasminogen Activators - metabolism ; Plasminogen Inactivators - metabolism ; Tumor Necrosis Factor-alpha - pharmacology ; Umbilical Veins - cytology</subject><ispartof>Thrombosis research, 1995-03, Vol.77 (5), p.431-440</ispartof><rights>1995</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-7d0116fc4f5d15cde3bf59d392eddf4f95418eb798c362232bb683c0778b2d0a3</citedby><cites>FETCH-LOGICAL-c386t-7d0116fc4f5d15cde3bf59d392eddf4f95418eb798c362232bb683c0778b2d0a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3459877$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7778058$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arnman, Veronika</creatorcontrib><creatorcontrib>Stemme, Sten</creatorcontrib><creatorcontrib>Rymo, Lars</creatorcontrib><creatorcontrib>Risberg, Bo</creatorcontrib><title>Interferon-γ modulates the fibrinolytic response in cultured human endothelial cells</title><title>Thrombosis research</title><addtitle>Thromb Res</addtitle><description>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-α (TNFα) 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, TNFα, interferon-γ (IFN-γ) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNFα 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 TNFα were modulated by IFN-γ but not by IL-6. The increased expression of u-PA after stimulation with TNFα was reduced by IFN-γ. In contrast, TNFα-induced expression of PAI-2 was synergistically increased by addition of IFN-γ. These effects of IFN-γ represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blood coagulation. Blood cells</subject><subject>Cells, Cultured</subject><subject>endothelial cells</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>fibrinolysis</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>General aspects, investigation methods, hemostasis, fibrinolysis</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>inflammatory cytokines</subject><subject>Interferon-gamma - pharmacology</subject><subject>Interleukin-6 - pharmacology</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Molecular and cellular biology</subject><subject>plasminogen activator</subject><subject>plasminogen activator inhibitor</subject><subject>Plasminogen Activators - drug effects</subject><subject>Plasminogen Activators - metabolism</subject><subject>Plasminogen Inactivators - metabolism</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><subject>Umbilical Veins - cytology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><recordid>eNp9kM1q3DAURkVoSSbTvkECWpSSLtxIlmVJm0AJ_QkEuknWQpauiIIsTSW7kOfqe_SZameGWXZ1L9zzXT4OQheUfKaE9teEdKphspNXin9STArV8BO0oevSdqJ9gzZH5Ayd1_pMCBVU8VN0KoSQhMsNerxLExQPJafm7x88ZjdHM0HF0xNgH4YSUo4vU7C4QN3lVAGHhO0cp7mAw0_zaBKG5PLCx2AithBjfYfeehMrvD_MLXr89vXh9kdz__P73e2X-8Yy2U-NcITS3tvOc0e5dcAGz5VjqgXnfOcV76iEQShpWd-2rB2GXjJLlvJD64hhW_Rx_3dX8q8Z6qTHUNcGJkGeqxaCtYwRuoDdHrQl11rA610JoykvmhK92tSrKr2q0orrV5uaL7HLw_95GMEdQwd9y_3D4W6qNdEXk2yoR4x1XMmlwxbd7DFYXPwOUHS1AZIFFwrYSbsc_t_jH56uksI</recordid><startdate>19950301</startdate><enddate>19950301</enddate><creator>Arnman, Veronika</creator><creator>Stemme, Sten</creator><creator>Rymo, Lars</creator><creator>Risberg, Bo</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19950301</creationdate><title>Interferon-γ modulates the fibrinolytic response in cultured human endothelial cells</title><author>Arnman, Veronika ; Stemme, Sten ; Rymo, Lars ; Risberg, Bo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-7d0116fc4f5d15cde3bf59d392eddf4f95418eb798c362232bb683c0778b2d0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blood coagulation. Blood cells</topic><topic>Cells, Cultured</topic><topic>endothelial cells</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>fibrinolysis</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>General aspects, investigation methods, hemostasis, fibrinolysis</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>inflammatory cytokines</topic><topic>Interferon-gamma - pharmacology</topic><topic>Interleukin-6 - pharmacology</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Molecular and cellular biology</topic><topic>plasminogen activator</topic><topic>plasminogen activator inhibitor</topic><topic>Plasminogen Activators - drug effects</topic><topic>Plasminogen Activators - metabolism</topic><topic>Plasminogen Inactivators - metabolism</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>Umbilical Veins - cytology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arnman, Veronika</creatorcontrib><creatorcontrib>Stemme, Sten</creatorcontrib><creatorcontrib>Rymo, Lars</creatorcontrib><creatorcontrib>Risberg, Bo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Thrombosis research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arnman, Veronika</au><au>Stemme, Sten</au><au>Rymo, Lars</au><au>Risberg, Bo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interferon-γ modulates the fibrinolytic response in cultured human endothelial cells</atitle><jtitle>Thrombosis research</jtitle><addtitle>Thromb Res</addtitle><date>1995-03-01</date><risdate>1995</risdate><volume>77</volume><issue>5</issue><spage>431</spage><epage>440</epage><pages>431-440</pages><issn>0049-3848</issn><eissn>1879-2472</eissn><coden>THBRAA</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>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-α (TNFα) 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, TNFα, interferon-γ (IFN-γ) or interleukin-6 (IL-6) alone or in combinations. Stimulation with LPS or TNFα 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 TNFα were modulated by IFN-γ but not by IL-6. The increased expression of u-PA after stimulation with TNFα was reduced by IFN-γ. In contrast, TNFα-induced expression of PAI-2 was synergistically increased by addition of IFN-γ. These effects of IFN-γ represent additional mechanisms by which inflammatory mediators may turn the fibrinolytic potential of the endothelium in a prothrombotic direction.</abstract><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>7778058</pmid><doi>10.1016/0049-3848(95)93879-5</doi><tpages>10</tpages></addata></record> |
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| ispartof | Thrombosis research, 1995-03, Vol.77 (5), p.431-440 |
| issn | 0049-3848 1879-2472 |
| language | eng |
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| source | ScienceDirect Journals |
| subjects | Adult Biological and medical sciences Blood coagulation. Blood cells Cells, Cultured endothelial cells Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Enzyme-Linked Immunosorbent Assay fibrinolysis Fundamental and applied biological sciences. Psychology General aspects, investigation methods, hemostasis, fibrinolysis Humans Infant, Newborn inflammatory cytokines Interferon-gamma - pharmacology Interleukin-6 - pharmacology Lipopolysaccharides - pharmacology Molecular and cellular biology plasminogen activator plasminogen activator inhibitor Plasminogen Activators - drug effects Plasminogen Activators - metabolism Plasminogen Inactivators - metabolism Tumor Necrosis Factor-alpha - pharmacology Umbilical Veins - cytology |
| title | Interferon-γ modulates the fibrinolytic response in cultured human endothelial cells |
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