{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:03:36Z","timestamp":1790327016564,"version":"4.1.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2001,2,1]],"date-time":"2001-02-01T00:00:00Z","timestamp":980985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2001,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The interaction of<jats:italic>Listeria monocytogenes<\/jats:italic>with endothelial cells represents a crucial step in the pathogenesis of listeriosis. Incubation of human umbilical vein endothelial cells (HUVEC) with wild-type<jats:italic>L. monocytogenes<\/jats:italic>(EGD) provoked immediate strong NO synthesis, attributable to listerial presentation of listeriolysin O (LLO), as the NO release was missed upon employment of a deletion mutant for LLO (EGD<jats:italic>hly<\/jats:italic>mutant) and was reproduced by purified LLO. Studies of conditions lacking extracellular Ca<jats:sup>2+<\/jats:sup>suggested LLO-elicited Ca<jats:sup>2+<\/jats:sup>flux as the underlying mechanism. In addition, HUVEC incubation with EGD turned out to be a potent stimulus for sustained (&gt;12-h) upregulation of proinflammatory cytokine generation (interleukin 6 [IL-6], IL-8, and granulocyte-macrophage colony-stimulating factor). Use of deletion mutants for LLO (EGD<jats:italic>hly<\/jats:italic>mutant), listerial phosphatidylinositol-specific phospholipase C (EGD<jats:italic>plcA<\/jats:italic>mutant), broad-spectrum phospholipase C (EGD<jats:italic>plcB<\/jats:italic>mutant) and internalin B (EGD<jats:italic>inlB<\/jats:italic>mutant), as well as purified LLO, identified LLO as largely responsible for the cytokine response. Endothelial cells responded with diacylglycerole and ceramide generation as well as nuclear translocation of NF-\u03baB to the stimulation with the LLO-producing strains EGD and<jats:italic>Listeria innocua<\/jats:italic>. The endothelial PC-phospholipase C inhibitor tricyclodecan-9-yl-xanthogenate as well as two independent inhibitors of NF-\u03baB activation, pyrolidine dithiocarbamate and caffeic acid phenethyl ester, suppressed both the NF-\u03baB translocation and the upregulation of cytokine synthesis. We conclude that<jats:italic>L. monocytogenes<\/jats:italic>is a potent stimulus of NO release and sustained upregulation of proinflammatory cytokine synthesis in human endothelial cells, both events being largely attributable to LLO presentation. LLO-induced transmembrane Ca<jats:sup>2+<\/jats:sup>flux as well as a sequence of endothelial phospholipase activation and the appearance of diacylglycerole, ceramide, and NF-\u03baB are suggested as underlying host signaling events. These endothelial responses to<jats:italic>L. monocytogenes<\/jats:italic>may well contribute to the pathogenic sequelae in severe listerial infection and sepsis.<\/jats:p>","DOI":"10.1128\/iai.69.2.897-905.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:01:19Z","timestamp":1027764079000},"page":"897-905","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Human Endothelial Cell Activation and Mediator Release in Response to<i>Listeria monocytogenes<\/i>Virulence Factors"],"prefix":"10.1128","volume":"69","author":[{"given":"Frank","family":"Rose","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Internal Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven-Arne","family":"Zeller","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Internal Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinad","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Institute of Medical Microbiology,2 Justus Liebig University, Giessen, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Domann","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Institute of Medical Microbiology,2 Justus Liebig University, Giessen, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Machleidt","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Institute of Microbiology, University of Cologne, Cologne,3 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Kronke","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Institute of Microbiology, University of Cologne, Cologne,3 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Internal Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Grimminger","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Internal Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Sibelius","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Internal Medicine1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.4.11.2199284"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81318-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(96)00004-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.2.568-574.1992"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.1.259"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1656(95)00138-7"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"5305","DOI":"10.4049\/jimmunol.158.11.5305","article-title":"Listeria monocytogenes infection of cultured endothelial cells stimulates neutrophil adhesion and adhesion molecule expression","volume":"158","author":"Drevets D. 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