Inhibition of nuclear factor-kappa B induces inflammatory cell migration and exacerbates severe liver injury in hepatitis B virus transgenic mice.

Aim: Nuclear factor-kappa B (NF-kappaB) has a central role in co-ordinating the expression of a wide variety of genes that control the immune response and it is also recognized as an antiapoptotic transcription factor. In this study, we focused on the role of the NF-kappaB signaling pathway in liver injury induced in hepatitis B virus (HBV) transgenic mice.

Methods: A fulminant hepatitis model was created in mice by the adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) into HBV transgenic mice. We used an adenovirus expressing a mutant form of the IkappaB super-repressor (Ad5IkappaB), an NF-kappaB inhibitor, to inhibit the NF-kappaB signaling pathway.

Results: We observed that pretreatment with Ad5IkappaB increased the migration of inflammatory cells into the liver 6-24 h after a single intravenous injection of antigen-specific CTLs, in comparison to pretreatment with a control adenovirus. We also demonstrated that the presence of the NF-kappaB inhibitor exacerbated severe liver injury and hepatocellular apoptosis 24 h after the injection of the antigen-specific CTLs.

Conclusion: These results suggest that the inhibition of NF-kappaB activity induces severe fulminant hepatitis in HBV transgenic mice.