Liver-specific HBsAg transgenic mice are over-sensitive to Poly(I:C)-induced liver injury in NK cell- and IFN-γ-dependent manner☆
Received 7 December 2006; received in revised form 12 February 2007; accepted 22 February 2007. published online 19 March 2007.
Background/Aims
The role of natural killer (NK) cells in the development of hepatitis B virus (HBV)-associated liver injury remains obscure. In this study, we elucidated the role of NK cells in liver injury of HBsAg transgenic mice (HBs-B6), a mimic of human healthy chronic HBsAg carriers, triggered by polyinosinic:polycytidylic acid [Poly(I:C)].
Methods
HBs-B6 or wild B6 mice were intraperitoneally injected with Poly(I:C) at different doses. Liver injury was evaluated by serum transaminase activity and histopathologic changes.
Results
HBs-B6 mice were over-sensitive to Poly(I:C)-induced liver injury, which was absolutely dependent on the presence of NK cells and IFN-γ produced by intrahepatic NK cells. Much stronger IFN-γ receptor expression was observed on hepatocytes of HBs-B6 mice, which was significantly enhanced by Poly(I:C) injection. Treatment with IFN-γ in vitro triggered much higher activation of downstream signals (pSTAT1-IRF-1) in hepatocytes of HBs-B6 mice. Depletion of Kupffer cells and neutralization of endogenous IL-12 did not affect Poly(I:C)-induced over-sensitive liver injury in HBs-B6 mice.
Conclusions
NK cells played a critical role in an IFN-γ dependent, Kupffer cell- and IL-12-independent manner in over-sensitive liver injury triggered by Poly(I:C) in murine chronic HBsAg carriers.
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, 443 Huangshan Road, Hefei City, Anhui 230027, PR China
Corresponding authors.
☆ The authors declare that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
ABSTRACT