Role of monokine induced by interferon-γ in liver injury induced by hepatitis B virus in mice.
The chemokine monokine induced by interferon-γ (Mig) is involved in the recruitment of inflammatory cells and liver injury during hepatitis B virus (HBV) infection. HBV protein X contributes to Mig expression in vitro by activation of nuclear factor (NF)-κB; however, the molecular mechanisms by which HBV induces Mig expression in vivo are unknown. In this paper, we established a mouse model for HBV study by tail vein injection of HBV genome-containing adenovirus vectors. Host immune response to the secreted hepatitis B surface antigen and e antigen was detected and serum alanine aminotransferase (ALT) was elevated at different time points. We also demonstrated that peripheral and intrahepatic Mig expression was increased after Ad-HBV infection. This was followed by inflammatory cell migration and formation of inflammatory foci in the liver. In addition, NF-κB p65 subunit translocated from the cytoplasm to the nucleus, and phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were to some extent phosphorylated after HBV injection. Following tail vein injection of Mig siRNA/in vivo-jetPEI-Gal complex, Mig expression was partially suppressed, inflammatory cell migration was inhibited, serum level of ALT were reduced. In conclusion, through NF-κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3-kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo.
Division of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Y J
YJ
Xia
D
D
Zeng
L M
LM
Xia
F
F
Yu
H H
HH
Lin
L
L
Zhou
D A
DA
Tian
M
M
Liu
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology / Q000472:pathogenicity*; D007371:Interferon-gamma / Q000378:metabolism*; D008099:Liver / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015846:Monokines / Q000378:metabolism*
D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D015846:Monokines; D007371:Interferon-gamma; D000410:Alanine Transaminase