Biopolym. Cell. 2009; 25(2):145-149.
http://dx.doi.org/10.7124/bc.0007D8
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

Abstract

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
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