Biopolymers and cell. 2009; 25 (2): 145 - 149

 

 

Interferon a and protein kinase R during rat liver restoration after partial hepatectomy

 

M.M. Perepelyuk, A. V. Kuklin, Ia. V. Shcherba, B. T. Tokovenko, N. V. Makogon1, A. Gogler2, S. Szala2, M. Yu. Obolenskaya

 

 

Institute of Molecular Biology and Genetics of NAS of Ukraine, 150 Zabolotnogo Str., Kiev, Ukraine 03143;
1 Institute of physiolology named by A.A.Bogomolets, NAS of Ukraine, 4 Academician Bogomoltsa Str., Kiev, Ukraine, 01024;
2 Cancer Centre, Maria Sklodowska-Curie Memorial Institute, Branch Gliwice, 15 Wybrzeże Armii Krajowej Str., 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 IFNa, 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, cor- respondingly. After PHE a short-term increase in IFNa expression is revealed in Kupffer cells. In hepatocytes PKR – mRNA up-regulation takes place, followed by an increase in IFNa – mRNA production. Taking into account the dual function of PKR as a target and inducer of IFNa, we suggest that secretion of IFNa 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 IFNa gene expression. After laparatomy the IFN 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 IFN system that is characteristic of the liver restoration and acute phase reaction.

 

Keywords: interferon a, protein kinase R, liver regeneration.