IFN-gamma inhibits thrombin- and endotoxin-induced plasminogen activator inhibitor type 1 in human endothelial cells
The plasmin/plasminogen system of enzymes may be involved in leukocyte migration through the endothelial cell layer of the vascular wall during inflammatory processes associated with vascular injury, atherosclerosis, and sepsis. Synthesis of plasminogen activator inhibitor type 1 (PAI-1) by the endo...
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Veröffentlicht in: | The Journal of immunology (1950) 1996-09, Vol.157 (6), p.2610-2617 |
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creator | Gallicchio, M Hufnagl, P Wojta, J Tipping, P |
description | The plasmin/plasminogen system of enzymes may be involved in leukocyte migration through the endothelial cell layer of the vascular wall during inflammatory processes associated with vascular injury, atherosclerosis, and sepsis. Synthesis of plasminogen activator inhibitor type 1 (PAI-1) by the endothelium may protect these cells and the subendothelial cell matrix from excessive degradation and retard leukocyte migration. We report in this work for the first time the down-regulation of both basal and thrombin- or endotoxin-induced PAI-1 in cultured human endothelial cells by the activated T cell product, IFN-gamma. Down-regulation of basal and thrombin- or endotoxin-induced endothelial PAI-1 protein by IFN-gamma was found to be both time and dose dependent. Decreases of up to 71% relative to thrombin- or endotoxin-treated controls, using an optimal IFN-gamma concentration of between 20 and 200 U/ml, were found for human macrovascular and microvascular endothelial cells. However, IFN-gamma did not appear to affect IL-1 alpha- and TNF-alpha-induced levels of PAI-1 protein or mRNA in these cells. Northern blot analysis paralleled protein results, showing decreases in specific endothelial cell thrombin- or LPS-induced PAI-1 mRNA expression, respectively, after incubation with IFN-gamma for 24 h. These results suggest a means by which the migration of circulating leukocytes through endothelial cell layers during inflammation may be facilitated. |
doi_str_mv | 10.4049/jimmunol.157.6.2610 |
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Synthesis of plasminogen activator inhibitor type 1 (PAI-1) by the endothelium may protect these cells and the subendothelial cell matrix from excessive degradation and retard leukocyte migration. We report in this work for the first time the down-regulation of both basal and thrombin- or endotoxin-induced PAI-1 in cultured human endothelial cells by the activated T cell product, IFN-gamma. Down-regulation of basal and thrombin- or endotoxin-induced endothelial PAI-1 protein by IFN-gamma was found to be both time and dose dependent. Decreases of up to 71% relative to thrombin- or endotoxin-treated controls, using an optimal IFN-gamma concentration of between 20 and 200 U/ml, were found for human macrovascular and microvascular endothelial cells. However, IFN-gamma did not appear to affect IL-1 alpha- and TNF-alpha-induced levels of PAI-1 protein or mRNA in these cells. Northern blot analysis paralleled protein results, showing decreases in specific endothelial cell thrombin- or LPS-induced PAI-1 mRNA expression, respectively, after incubation with IFN-gamma for 24 h. These results suggest a means by which the migration of circulating leukocytes through endothelial cell layers during inflammation may be facilitated.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.157.6.2610</identifier><identifier>PMID: 8805664</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Cells, Cultured ; Down-Regulation - drug effects ; Endothelium, Vascular - cytology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Endotoxins - pharmacology ; Humans ; Interferon-gamma - pharmacology ; Plasminogen Activator Inhibitor 1 - biosynthesis ; Plasminogen Activator Inhibitor 1 - metabolism ; Serine Proteinase Inhibitors - biosynthesis ; Serine Proteinase Inhibitors - metabolism ; Thrombin - pharmacology</subject><ispartof>The Journal of immunology (1950), 1996-09, Vol.157 (6), p.2610-2617</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-563b42b540cdc31590bc712c32987199be340cac0bd33d3b25146ee3f1dd6d333</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8805664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gallicchio, M</creatorcontrib><creatorcontrib>Hufnagl, P</creatorcontrib><creatorcontrib>Wojta, J</creatorcontrib><creatorcontrib>Tipping, P</creatorcontrib><title>IFN-gamma inhibits thrombin- and endotoxin-induced plasminogen activator inhibitor type 1 in human endothelial cells</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>The plasmin/plasminogen system of enzymes may be involved in leukocyte migration through the endothelial cell layer of the vascular wall during inflammatory processes associated with vascular injury, atherosclerosis, and sepsis. Synthesis of plasminogen activator inhibitor type 1 (PAI-1) by the endothelium may protect these cells and the subendothelial cell matrix from excessive degradation and retard leukocyte migration. We report in this work for the first time the down-regulation of both basal and thrombin- or endotoxin-induced PAI-1 in cultured human endothelial cells by the activated T cell product, IFN-gamma. Down-regulation of basal and thrombin- or endotoxin-induced endothelial PAI-1 protein by IFN-gamma was found to be both time and dose dependent. Decreases of up to 71% relative to thrombin- or endotoxin-treated controls, using an optimal IFN-gamma concentration of between 20 and 200 U/ml, were found for human macrovascular and microvascular endothelial cells. However, IFN-gamma did not appear to affect IL-1 alpha- and TNF-alpha-induced levels of PAI-1 protein or mRNA in these cells. Northern blot analysis paralleled protein results, showing decreases in specific endothelial cell thrombin- or LPS-induced PAI-1 mRNA expression, respectively, after incubation with IFN-gamma for 24 h. These results suggest a means by which the migration of circulating leukocytes through endothelial cell layers during inflammation may be facilitated.</description><subject>Cells, Cultured</subject><subject>Down-Regulation - drug effects</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endotoxins - pharmacology</subject><subject>Humans</subject><subject>Interferon-gamma - pharmacology</subject><subject>Plasminogen Activator Inhibitor 1 - biosynthesis</subject><subject>Plasminogen Activator Inhibitor 1 - metabolism</subject><subject>Serine Proteinase Inhibitors - biosynthesis</subject><subject>Serine Proteinase Inhibitors - metabolism</subject><subject>Thrombin - pharmacology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUctOGzEUtSqqEKBfUFXyiq4m-DH2zCwrRFokVDZlbfmVjJEfYexp4O_rKKHqrqt773npSgeAzxitWtQON88uhDkmv8KsW_EV4Rh9AEvMGGo4R_wMLBEipMEd787BRc7PCCGOSLsAi75HjPN2Ccr9-mezlSFI6OLolCsZlnFKQbnYQBkNtNGkkl7r6aKZtTVw52UOLqatjVDq4n7LkqZ3e93K285CXAE4zkHGY8JovZMeaut9vgIfN9Jn--k0L8HT-u7X7Y_m4fH7_e23h0a3ZCgN41S1RLEWaaMpZgNSusNEUzL0HR4GZWmlpEbKUGqoIgy33Fq6wcbwCtFLcH3M3U3pZba5iODy4QMZbZqz6HpKMO_-L8SsRxzjoQrpUainlPNkN2I3uSCnN4GROJQi3kupnk5wcSilur6c4mcVrPnrObVQ-a9HfnTbce8mK3KQ3lc1Fvv9_p-kP6vnmVM</recordid><startdate>19960915</startdate><enddate>19960915</enddate><creator>Gallicchio, M</creator><creator>Hufnagl, P</creator><creator>Wojta, J</creator><creator>Tipping, P</creator><general>Am Assoc Immnol</general><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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19960915</creationdate><title>IFN-gamma inhibits thrombin- and endotoxin-induced plasminogen activator inhibitor type 1 in human endothelial cells</title><author>Gallicchio, M ; Hufnagl, P ; Wojta, J ; Tipping, P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-563b42b540cdc31590bc712c32987199be340cac0bd33d3b25146ee3f1dd6d333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Cells, Cultured</topic><topic>Down-Regulation - drug effects</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endotoxins - pharmacology</topic><topic>Humans</topic><topic>Interferon-gamma - pharmacology</topic><topic>Plasminogen Activator Inhibitor 1 - biosynthesis</topic><topic>Plasminogen Activator Inhibitor 1 - metabolism</topic><topic>Serine Proteinase Inhibitors - biosynthesis</topic><topic>Serine Proteinase Inhibitors - metabolism</topic><topic>Thrombin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gallicchio, M</creatorcontrib><creatorcontrib>Hufnagl, P</creatorcontrib><creatorcontrib>Wojta, J</creatorcontrib><creatorcontrib>Tipping, P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gallicchio, M</au><au>Hufnagl, P</au><au>Wojta, J</au><au>Tipping, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IFN-gamma inhibits thrombin- and endotoxin-induced plasminogen activator inhibitor type 1 in human endothelial cells</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1996-09-15</date><risdate>1996</risdate><volume>157</volume><issue>6</issue><spage>2610</spage><epage>2617</epage><pages>2610-2617</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The plasmin/plasminogen system of enzymes may be involved in leukocyte migration through the endothelial cell layer of the vascular wall during inflammatory processes associated with vascular injury, atherosclerosis, and sepsis. Synthesis of plasminogen activator inhibitor type 1 (PAI-1) by the endothelium may protect these cells and the subendothelial cell matrix from excessive degradation and retard leukocyte migration. We report in this work for the first time the down-regulation of both basal and thrombin- or endotoxin-induced PAI-1 in cultured human endothelial cells by the activated T cell product, IFN-gamma. Down-regulation of basal and thrombin- or endotoxin-induced endothelial PAI-1 protein by IFN-gamma was found to be both time and dose dependent. Decreases of up to 71% relative to thrombin- or endotoxin-treated controls, using an optimal IFN-gamma concentration of between 20 and 200 U/ml, were found for human macrovascular and microvascular endothelial cells. However, IFN-gamma did not appear to affect IL-1 alpha- and TNF-alpha-induced levels of PAI-1 protein or mRNA in these cells. Northern blot analysis paralleled protein results, showing decreases in specific endothelial cell thrombin- or LPS-induced PAI-1 mRNA expression, respectively, after incubation with IFN-gamma for 24 h. These results suggest a means by which the migration of circulating leukocytes through endothelial cell layers during inflammation may be facilitated.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>8805664</pmid><doi>10.4049/jimmunol.157.6.2610</doi><tpages>8</tpages></addata></record> |
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subjects | Cells, Cultured Down-Regulation - drug effects Endothelium, Vascular - cytology Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Endotoxins - pharmacology Humans Interferon-gamma - pharmacology Plasminogen Activator Inhibitor 1 - biosynthesis Plasminogen Activator Inhibitor 1 - metabolism Serine Proteinase Inhibitors - biosynthesis Serine Proteinase Inhibitors - metabolism Thrombin - pharmacology |
title | IFN-gamma inhibits thrombin- and endotoxin-induced plasminogen activator inhibitor type 1 in human endothelial cells |
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