{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T17:03:35Z","timestamp":1772039015387,"version":"3.50.1"},"reference-count":33,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2012,2,13]],"date-time":"2012-02-13T00:00:00Z","timestamp":1329091200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Innate Immun"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:p> We evaluated expression of TLR2, TLR4 and proinflammatory genes [NF-\u03baB, TNF-\u03b1, cyclooxygenase-2 (COX-2)] in liver samples of patients in different stages of liver disease. Fifteen patients with unexplained transaminases elevation (reference group), 22 with viral chronic hepatitis (hepatitis group), 14 with virus-induced severe fibrosis\/cirrhosis (cirrhosis group) and 10 with hepatocarcinoma (hepatocarcinoma group) were consecutively included in the study. Quantification of TLR2, TLR4, NF-\u03baB, TNF-\u03b1 and COX-2 mRNA was done by real-time RT-PCR and TLR2 and TLR4 protein expression was evaluated by immunohistochemistry. Compared with reference, TLR2 and TLR4 mRNA was increased in hepatitis (TLR2: 2.66\u2009\u00b1\u20090.69; TLR4: 3.11\u2009\u00b1\u20090.79; P\u2009&lt;\u20090.05) and cirrhosis (TLR2: 2.14\u2009\u00b1\u20090.5; TLR4: 1.74\u2009\u00b1\u20090.27; P\u2009&lt;\u20090.05) and decreased in hepatocarcinoma (TLR2: 0.48\u2009\u00b1\u20090.15; TLR4: 0.54\u2009\u00b1\u20090.10; P\u2009&lt;\u20090.05). This associated with increased TNF-\u03b1 and COX-2 mRNA in hepatitis (TNF-\u03b1: 3.24\u2009\u00b1\u20090.79; COX-2: 2.47\u2009\u00b1\u20090.36; P\u2009&lt;\u20090.05) and cirrhosis (TNF-\u03b1: 1.73\u2009\u00b1\u20090.28; COX-2: 1.8\u2009\u00b1\u20090.35, P\u2009&lt;\u20090.05), whereas NF-\u03baB mRNA was increased in hepatitis (2.42\u2009\u00b1\u20090.31; P\u2009&lt;\u20090.05) and unchanged in cirrhosis (1.34\u2009\u00b1\u20090.17; P\u2009=\u20090.3). Hepatocarcinoma presented increased COX-2 mRNA (1.63\u2009\u00b1\u20090.15; P\u2009&lt;\u20090.05) and maintained (at decreased levels) mRNA of NF-\u03baB (0.52\u2009\u00b1\u20090.12) and TNF-\u03b1 (0.52\u2009\u00b1\u20090.12; P\u2009&lt;\u20090.05, all genes). Immunohistochemistry confirmed increased expression of TLR2 and TLR4 in hepatitis and cirrhosis and maintained expression in hepatocarcinoma. Upregulation of TLR2, TLR4 and their proinflammatory mediators is associated with virus-induced hepatic IFC sequence. <\/jats:p>","DOI":"10.1177\/1753425912436762","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T04:16:58Z","timestamp":1329193018000},"page":"700-708","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":56,"title":["Increased hepatic expression of TLR2 and TLR4 in the hepatic           inflammation-fibrosis-carcinoma sequence"],"prefix":"10.1177","volume":"18","author":[{"given":"Jo\u00e3o-Bruno","family":"Soares","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Porto,\r        Portugal"},{"name":"Braga Hospital, Portugal"}]},{"given":"Pedro","family":"Pimentel-Nunes","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto,\r        Portugal"},{"name":"Portuguese Oncology Institute, Portugal"}]},{"given":"Lu\u00eds","family":"Afonso","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute, Portugal"}]},{"given":"Carla","family":"Rolanda","sequence":"additional","affiliation":[{"name":"Braga Hospital, Portugal"},{"name":"Life and Health Sciences Research Institute,\r        University of Minho, Portugal"}]},{"given":"Paula","family":"Lopes","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute, Portugal"}]},{"suffix":"Jr","given":"Roberto","family":"Roncon-Albuquerque","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto,\r        Portugal"}]},{"given":"N\u00e1dia","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto,\r        Portugal"}]},{"given":"In\u00eas","family":"Boal-Carvalho","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto,\r        Portugal"}]},{"given":"Fernando","family":"Pardal","sequence":"additional","affiliation":[{"name":"Braga Hospital, Portugal"}]},{"given":"Susana","family":"Lopes","sequence":"additional","affiliation":[{"name":"S\u00e3o Jo\u00e3o Hospital, Portugal"}]},{"given":"Guilherme","family":"Macedo","sequence":"additional","affiliation":[{"name":"S\u00e3o Jo\u00e3o Hospital, Portugal"}]},{"given":"L\u00facio","family":"Lara-Santos","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute, Portugal"}]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute, Portugal"},{"name":"Porto Faculty of Medicine, Portugal"}]},{"given":"Lu\u00eds","family":"Moreira-Dias","sequence":"additional","affiliation":[{"name":"Braga Hospital, Portugal"}]},{"given":"Raquel","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Braga Hospital, Portugal"}]},{"given":"M\u00e1rio","family":"Dinis-Ribeiro","sequence":"additional","affiliation":[{"name":"Portuguese Oncology Institute, Portugal"},{"name":"Institute of Biomedical Sciences Abel Salazar,\r        University of Porto, Portugal"}]},{"given":"Adelino F","family":"Leite-Moreira","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Porto,\r        Portugal"}]}],"member":"179","published-online":{"date-parts":[[2012,2,13]]},"reference":[{"key":"bibr1-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21802"},{"key":"bibr2-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22306"},{"key":"bibr3-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2008.156307"},{"key":"bibr4-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1517\/14728221003642027"},{"key":"bibr5-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-010-9219-x"},{"key":"bibr6-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.015"},{"key":"bibr7-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-019307"},{"key":"bibr8-1753425912436762","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.2.554"},{"key":"bibr9-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.886"},{"key":"bibr10-1753425912436762","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i4.403"},{"key":"bibr11-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20632"},{"key":"bibr12-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2010.02251.x"},{"key":"bibr13-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00577.x"},{"key":"bibr14-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"bibr15-1753425912436762","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.06.017"},{"key":"bibr16-1753425912436762","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.8242"},{"key":"bibr17-1753425912436762","first-page":"a99","volume":"7","author":"Spitzer 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