{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:15:17Z","timestamp":1788869717182,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T00:00:00Z","timestamp":1400025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Australian National Health and Medical Research Council, NHMRC","award":["1011649"],"award-info":[{"award-number":["1011649"]}]},{"name":"Australian National Health and Medical Research Council, NHMRC","award":["1003707"],"award-info":[{"award-number":["1003707"]}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"crossref","award":["1019921"],"award-info":[{"award-number":["1019921"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2014,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Tenascin\u2010C (Tn\u2010C) is an endogenous ligand of toll\u2010like receptor\u20104 (TLR\u20104); a key signalling molecule associated with chronic inflammatory conditions. Both Tn\u2010C and TLR\u20104 are increased in unstable human atheroma, but their effects on local inflammatory conditions have not been investigated. The aim of the present study was to investigate the association and functional implications of Tn\u2010C\/TLR\u20104 signalling in large artery atherosclerotic stroke. Plasma Tn\u2010C was measured by ELISA and found to be higher in recent stroke patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009336; median 12.77 \u00b5g\/mL, inter\u2010quartile range 10.23\u201315.74 \u00b5g\/mL) than in controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009321; median 11.31 \u00b5g\/mL, inter\u2010quartile range 8.89\u201313.90 \u00b5g\/mL),\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001. Plasma Tn\u2010C was also independently positively associated with stroke (odds ratio for highest Tn\u2010C quartile 2.27, 95% confidence interval 1.37\u20133.76). Assessment of Tn\u2010C associated chronic cytokine secretion was performed\n                    <jats:italic>in vitro<\/jats:italic>\n                    using paired, human, macroscopically disease matched, carotid atheroma tissue biopsies obtained from five patients undergoing carotid endarterectomy. A 4\u2010day incubation with specific Tn\u2010C blocking antibodies (Abs) increased secretion of TLR\u20104\u2010associated cytokines, interleukin (IL)\u20108, IL\u20101\u03b2, tumour necrosis factor and C\u2010C motif chemokine (CCL)3 and expression of TLR\u20104 in the tissue. These results suggest with Tn\u2010C blockade another endogenous TLR\u20104 ligand upregulates TLR\u20104 expression and subsequent cytokine secretion. Titration of the Tn\u2010C Abs also dose dependently increased secretion of IL\u20106, IL\u20108, IL\u20101\u03b2, and CCL3 in mixed, healthy, primary vascular cell culture. In summary, circulating concentrations of Tn\u2010C are higher in patients with a recent history of atherosclerotic stroke and may play an anti\u2010inflammatory role by reducing pro\u2010inflammatory cytokine release from atheroma. \u00a9 2014 BioFactors, 40(4):448\u2013457, 2014\n                  <\/jats:p>","DOI":"10.1002\/biof.1170","type":"journal-article","created":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T01:41:05Z","timestamp":1400031665000},"page":"448-457","source":"Crossref","is-referenced-by-count":10,"title":["<scp>Tenascin\u2010C<\/scp>\n                    is increased in atherothrombotic stroke patients and has an anti\u2010inflammatory effect in the human carotid artery"],"prefix":"10.1002","volume":"40","author":[{"given":"Paula","family":"Clancy","sequence":"first","affiliation":[{"name":"Health practitioners And Researchers Together\u2010Blood Endothelium And Tissue (HART\u2010BEAT) Australian Institute for Tropical Health and Medicine, School of Veterinary and Biomedical Sciences, James Cook University Townsville QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa F.","family":"Lincz","sequence":"additional","affiliation":[{"name":"Hunter Haematology Research Group Calvary Mater Newcastle Hospital Waratah NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Maguire","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medicine School of Nursing and Midwifery, University of Newcastle, University Drive Callaghan NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"McEvoy","sequence":"additional","affiliation":[{"name":"University of Newcastle, School of Medicine and Public Health HMRI Building Lookout Rd New Lambton NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Koblar","sequence":"additional","affiliation":[{"name":"Stroke Research Programme School of Medicine The Queen Elizabeth Hospital (TQEH) Campus Adelaide University Woodville Sth South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Golledge","sequence":"additional","affiliation":[{"name":"The Vascular Biology Unit Queensland Research Centre for Peripheral Vascular Disease School of Medicine and Dentistry James Cook University Townsville QLD Australia"},{"name":"Department of Vascular and Endovascular Surgery The Townsville Hospital Townsville QLD Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,5,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901143400207"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/35025203"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00238-0"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01323"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043430"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00024.2005"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.10.5901"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc5001.100631"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.106.139253"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403249101"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-007-1001-1"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000089015.51603.CC"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00048.2003"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2006.10.008"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00305.2005"},{"key":"e_1_2_6_17_1","first-page":"501","article-title":"Effects of peroxisome proliferator\u2010activated receptor ligands in modulating tissue factor and tissue factor pathway inhibitor in acutely symptomatic carotid atheromas","volume":"35","author":"Golledge J.","year":"2007","journal-title":"Stroke"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1987"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.52.32798"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53809-6"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1242\/jcs.110.13.1513","article-title":"Concerted action of tenascin\u2010C domains in cell adhesion, anti\u2010adhesion and promotion of neurtite outgrowth","volume":"110","author":"Fischer D.","year":"1997","journal-title":"J. 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