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TitleIncreased hepatic expression of TLR2 and TLR4 in the hepatic inflammation-fibrosis-carcinoma sequence
Author(s)Soares, João Bruno
Nunes, Pedro Pimentel
Afonso, Luís
Rolanda, Carla
Lopes, Paula
Roncon-Albuquerque, R.
Gonçalves, Nádia
Carvalho, Inês Boal
Pardal, Fernando
Lopes, Susana
Henrique, Rui
Dias, Rui Moreira
Gonçalves, Raquel
Ribeiro, Mário Dinis
Moreira, Adelino F. Leite
KeywordsChronic hepatitis
Issue date2012
PublisherSAGE Publications
JournalInnate Immunity
Abstract(s)We evaluated expression of TLR2, TLR4 and proinflammatory genes [NF-?B, TNF-a, 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-?B, TNF-a 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-a and COX-2 mRNA in hepatitis (TNF-a: 3.24?±?0.79; COX-2: 2.47?±?0.36; P?<?0.05) and cirrhosis (TNF-a: 1.73?±?0.28; COX-2: 1.8?±?0.35, P?<?0.05), whereas NF-?B 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-?B (0.52?±?0.12) and TNF-a (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.
DescriptionPublicado em "Innate Immunity". ISSN 1753-4259, vol. 18, n.º 5 (2012), p. 700-708
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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