Biopolym. Cell. 2009; 25(2):145-149.
Short Communications
Interferon α and protein kinase R during rat liver restoration after partial hepatectomy
1Perepelyuk M. M., 1Kuklin A. V., 2Shcherba Ia. V., 1Tokovenko B. T., 2Makogon N. V., 3Gogler A., 3Szala S., 1Obolenskaya M. Yu.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Bogomoletz Institute of Physiology, NAS of Ukraine
    4, Bogomolets Str., Kyiv, Ukraine, 01024
  3. Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology
    Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland


The paper is devoted to validation of our hypothesis concerning an obligatory involvement of innate immune response in a liver transition from quiescence to proliferation. Our research is focused on the expression of IFNα, its receptor (first subunit) and its target – protein kinase R (PKR) during first 12 hours after regenerative stimulus. Two models were used – rat liver after partial hepatectomy (PHE) and after laparatomy, that imitate transition of inactive liver cells to proliferation and acute phase response as a component of liver response to PHE, correspondingly. After PHE a short-term increase in IFNα expression is revealed in Kupffer cells. In hepatocytes PKR – mRNA up-regulation takes place, followed by an increase in IFNα – mRNA production. Taking into account the dual function of PKR as a target and inducer of IFNα, we suggest that secretion of IFNα by Kupffer cells leads to the activation of PKR gene expression in hepatocytes, in which the product of PKR gene in its turn provokes an increase in the IFNα gene expression. After laparatomy the IFNα expression is down-regulated in Kupffer cells and hepatocytes. The expression of PKR – gene is opposite to that, observed after PHE – the level of PKR-RNA decreases in hepatocytes and transiently increases in Kupffer cells. PKR protein is detected in nuclei and cytoplasm in hepatocytes in intact liver and liver after laparatomy while it is concentrated in cytoplasm after 6 hours post-PHE, releasing nuclei from antigen. The expression of all investigated genes is cell-specific. It reveals respectively the activation and inhibition of IFNα system that is characteristic of the liver restoration and acute phase reaction.
Keywords: interferon α, protein kinase R, liver regeneration


[1] Perepelyuk M., Slonchak A., Sazonova L., Gubar O., Yakunchikova O., Obolenskaya M. Expression of genes, which encode IFN alpha, its receptor, protein kinase R and ribonuclease L in the intact and regenerating rat liver. Sci. proc. of NaUKMA Biol. and Ecol. 2005; 43:25–33.
[2] Strey C. W., Markiewski M., Mastellos D., Tudoran R., Spruce L., Greenbaum L., Lambris J. The proinflammatory mediators C3a and C5a are essential for liver regeneration J. Exp. Med 2003 198, N 6:913–923.
[3] Decker K. Biologically active products of stimulated liver macrophages (Kupffer cells) Eur. J. Biochem 1990 192, N 2: 245–261.
[4] Garcia M. A., Gil J., Ventoso I., Guerra S., Domingo E., Rivas C., Esteban M. Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action Microbiol. Mol. Biol. Rev 2006 70, N 4:1032–1060.
[5] Tokovenko B., Golda R., Protas O., Obolenskaya M., El'skaya A. COTRASIF: conservation-aided transcription factor binding site finder Nucleic Acids Res. 37(7):e49
[6] Higgins G. M., Anderson R. M. Experimental pathology of the liver. I. Restoration of the liver of the white rat following partial surgical removal. Arch. Pathol. 1931; 12(2):186–202.
[7] Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study J. Cell Biol 1969 43, N 3:506–520.
[8] Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium. Thiocyanate-phenol-chloroform extraction Anal. Biochem 1987 162:156–159.
[9] Sambrook J., Fritsch E. F., Maniatis T. Molecular cloning. Ed. N. Ford New York: Cold Spring Harbor Lab. press, 1989 Vol. 3 355 p.
[10] Decker T., Lohmann-Matthes M. L., Karck U., Peters T., Decker K. Comparative study of cytotoxicity, tumor necrosis factor, and prostaglandin release after stimulation of rat Kupffer cells, murine Kupffer cells, and murine inflammatory liver macrophages. J. Leukoc. Biol. 1989; 45(2):139–146.
[11] Perepelyuk M. M., Fedorchenko D. B., Rybalko S. L., Obolenskaya M. Yu. Interferon expression in the rat liver after partial hepatectomy Biopolym. Cell 2006 22, N 4:283–290.
[12] Marijanovic Z., Ragimbeau J., Kumar S., Fuchs S., Pellegrini S. TYK2 activity promotes ligand-induced IFNAR1 proteolysis Biochem. J 2006 397:31–38.
[13] Jeffrey I. W., Kadereit S., Meurs E. F., Metzger T., Bachmann M., Schwemmle M., Hovanessian A. G., Clemens M. Nuclear localization of the interferon-inducible protein kinase PKR in human cells and transfected mouse cells Exp. Cell. Res 1995 218, N 1:17–21.
[14] Drews J., Brawerman G. Alterations in the nature of ribonucleic acid synthesized in rat liver during regeneration and after cortisol administration J. Biol. Chem 1967 242, N 5 P. 801–808.