Alteration of intrahepatic cytokine expression and AP-1 activation in transgenic mice expressing hepatitis C virus core protein.

Abstract:

:Hepatitis C virus (HCV) infection often leads to the development of hepatocellular carcinoma (HCC), but its molecular mechanism has not been clearly elucidated. Previously, transgenic mice constitutively expressing HCV core protein have been shown to develop HCC, suggesting a pivotal role of the core protein in hepatocarcinogenesis. Here, we analyzed the expression of cytokines associated with a variety of cellular processes, including cell proliferation, in the mouse model for HCV-associated HCC to define the molecular events prior to oncogenesis. The expression of tumor necrosis factor-alpha and interleukin-1beta was increased at both protein and mRNA levels. In addition, the activities of c-Jun N-terminal kinase and activator protein-1 (AP-1), downstream effectors, were enhanced, while IkappaB kinase or nuclear factor-kappaB activities were not enhanced. Thus, the altered in vivo expression of cytokines with AP-1 activation in consequence to the core protein expression may contribute to hepatocarcinogenesis in persistent HCV infection.

journal_name

Virology

journal_title

Virology

authors

Tsutsumi T,Suzuki T,Moriya K,Yotsuyanagi H,Shintani Y,Fujie H,Matsuura Y,Kimura S,Koike K,Miyamura T

doi

10.1006/viro.2002.1702

subject

Has Abstract

pub_date

2002-12-20 00:00:00

pages

415-24

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042682202917022

journal_volume

304

pub_type

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