Increased hepatic expression of TLR2 and TLR4 in the hepatic inflammation-fibrosis-carcinoma sequence

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Soares, JB (Author) Other; Pedro Pimentel-Nunes (Author) FMUP; Afonso, L (Author) Other; Rolanda, C (Author) Other; Lopes, P (Author) Other; Roncon-Albuquerque R Jr (Author) FMUP; Goncalves, N (Author) Other; Boal Carvalho, I (Author) Other; Pardal, F (Author) Other; Lopes, S (Author) Other; Macedo G (Author) FMUP; Lucio Lara Santos (Author) ICBAS; henrique, rmf (Author) ICBAS; Moreira Dias, L (Author) Other; Goncalves, R (Author) Other; Mario Dinis Ribeiro (Author) FMUP; Leite-Moreira AF (Author) FMUP

Journal

Title: Innate immunity

Vol. 18

Pages: 700-708

ISSN: 1753-4259

Publisher: SAGE

Indexing

ISI Web of Knowledge - 52 Citations

Scopus - 62 Citations

Other information

Authenticus ID: P-002-4ZW

DOI: 10.1177/1753425912436762

Abstract (EN): We evaluated expression of TLR2, TLR4 and proinflammatory genes [NF-kappa B, TNF-alpha, 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-kappa B, TNF-alpha 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-alpha and COX-2 mRNA in hepatitis (TNF-alpha: 3.24 +/- 0.79; COX-2: 2.47 +/- 0.36; P < 0.05) and cirrhosis (TNF-alpha: 1.73 +/- 0.28; COX-2: 1.8 +/- 0.35, P < 0.05), whereas NF-kappa 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-kappa B (0.52 +/- 0.12) and TNF-alpha (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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9