title: Increased hepatic expression of TLR2 and TLR4 in the hepatic     inflammation-fibrosis-carcinoma sequence.
abstract: We evaluated expression of TLR2, TLR4 and proinflammatory genes [NF-κB, TNF-α,            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-κB, TNF-α 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 ± 0.69; TLR4: 3.11 ± 0.79; P < 0.05) and            cirrhosis (TLR2: 2.14 ± 0.5; TLR4: 1.74 ± 0.27; P < 0.05) and            decreased in hepatocarcinoma (TLR2: 0.48 ± 0.15; TLR4: 0.54 ± 0.10;            P < 0.05). This associated with increased TNF-α and COX-2 mRNA in            hepatitis (TNF-α: 3.24 ± 0.79; COX-2: 2.47 ± 0.36; P < 0.05) and            cirrhosis (TNF-α: 1.73 ± 0.28; COX-2: 1.8 ± 0.35, P < 0.05), whereas            NF-κB mRNA was increased in hepatitis (2.42 ± 0.31; P < 0.05) and            unchanged in cirrhosis (1.34 ± 0.17; P = 0.3). Hepatocarcinoma presented            increased COX-2 mRNA (1.63 ± 0.15; P < 0.05) and maintained (at            decreased levels) mRNA of NF-κB (0.52 ± 0.12) and TNF-α (0.52 ± 0.12;            P < 0.05, 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.
authors.affiliation: Faculty of Medicine, University of Porto, Porto, Portugal. jbrunosoares@yahoo.com
authors.forename: João-Bruno
authors.initials: JB
authors.lastname: Soares
authors.forename: Pedro
authors.initials: P
authors.lastname: Pimentel-Nunes
authors.forename: Luís
authors.initials: L
authors.lastname: Afonso
authors.forename: Carla
authors.initials: C
authors.lastname: Rolanda
authors.forename: Paula
authors.initials: P
authors.lastname: Lopes
authors.forename: Roberto
authors.initials: R
authors.lastname: Roncon-Albuquerque
authors.forename: Nádia
authors.initials: N
authors.lastname: Gonçalves
authors.forename: Inês
authors.initials: I
authors.lastname: Boal-Carvalho
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardal
authors.forename: Susana
authors.initials: S
authors.lastname: Lopes
authors.forename: Guilherme
authors.initials: G
authors.lastname: Macedo
authors.forename: Lúcio
authors.initials: L
authors.lastname: Lara-Santos
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.forename: Luís
authors.initials: L
authors.lastname: Moreira-Dias
authors.forename: Raquel
authors.initials: R
authors.lastname: Gonçalves
authors.forename: Mário
authors.initials: M
authors.lastname: Dinis-Ribeiro
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000821:virology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006509:Hepatitis B / Q000150:complications / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000276:immunology*; D006801:Humans; D008103:Liver Cirrhosis / Q000276:immunology* / Q000821:virology; D008113:Liver Neoplasms / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4