Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice - PubMed (original) (raw)

Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice

P N Gilles et al. J Virol. 1992 Jun.

Abstract

It is well known that several inflammatory cytokines can modulate hepatocellular gene expression in a complex physiological process known as the hepatic acute-phase response. Since hepatitis B virus (HBV) characteristically induces a vigorous lymphomononuclear inflammatory response in the liver during acute and chronic hepatitis, it is possible that hepatocellular HBV gene expression may also be modulated by one or more of the cytokines produced by these cells. Using bacterial lipopolysaccharide (LPS) as a surrogate inducer of inflammatory cytokines in vivo, we have tested this hypothesis in a transgenic mouse model system. In experiments with two independent transgenic mouse lineages that express the HBV envelope region under the control of either HBV or cellular promoters, we observed a 50 to 80% reduction in the hepatic steady-state content of a 2.1-kb HBV mRNA following administration of a single intraperitoneal dose of LPS. The regulatory influence of several inflammatory cytokines known to be induced by LPS was also examined in this system. The negative regulatory effect of LPS was consistently reproduced by the administration of a single nontoxic dose of tumor necrosis factor alpha, and it was occasionally observed following the administration of high doses of alpha interferon and interleukin-6, while no effect was detectable in response to high-dose interleukin-1 alpha or to gamma interferon. These observations suggest that tumor necrosis factor alpha and perhaps other cytokines may activate a heretofore unsuspected intracellular pathway that negatively regulates HBV gene expression. The intracellular mechanism(s) responsible for this effect and its pathophysiologic relevance remain to be elucidated.

PubMed Disclaimer

Cited by

Hepatitis B virus RNA-binding proteins associated with cytokine-induced clearance of viral RNA from the liver of transgenic mice.
Heise T, Guidotti LG, Cavanaugh VJ, Chisari FV. Heise T, et al. J Virol. 1999 Jan;73(1):474-81. doi: 10.1128/JVI.73.1.474-481.1999. J Virol. 1999. PMID: 9847353 Free PMC article.
HBV pathogenesis in animal models: recent advances on the role of platelets.
Iannacone M, Sitia G, Ruggeri ZM, Guidotti LG. Iannacone M, et al. J Hepatol. 2007 Apr;46(4):719-26. doi: 10.1016/j.jhep.2007.01.007. Epub 2007 Jan 29. J Hepatol. 2007. PMID: 17316876 Free PMC article. Review.
Hepatitis C virus superinfection in patients with chronic hepatitis B virus infection.
Liaw YF. Liaw YF. J Gastroenterol. 2002;37 Suppl 13:65-8. doi: 10.1007/BF02990102. J Gastroenterol. 2002. PMID: 12109669 Review.
Tumor necrosis factor-alpha induced by hepatitis B virus core mediating the immune response for hepatitis B viral clearance in mice model.
Tzeng HT, Tsai HF, Chyuan IT, Liao HJ, Chen CJ, Chen PJ, Hsu PN. Tzeng HT, et al. PLoS One. 2014 Jul 21;9(7):e103008. doi: 10.1371/journal.pone.0103008. eCollection 2014. PLoS One. 2014. PMID: 25047809 Free PMC article.

References

1. Anal Biochem. 1987 Apr;162(1):156-9 - PubMed
1. Proc Natl Acad Sci U S A. 1979 May;76(5):2222-6 - PubMed
1. J Clin Invest. 1986 Nov;78(5):1349-54 - PubMed
1. J Immunol. 1988 Jan 1;140(1):108-11 - PubMed
1. Biochem Pharmacol. 1988 Jul 1;37(13):2569-73 - PubMed

Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice - PubMed (original) (raw)