Molecular mechanisms of augmenter of liver regeneration as immunoregulator: its effect on interferon-γ expression in rat liver

• Published in: Digestive and liver disease Vol. 32; no. 3; pp. 217 - 225
• Main Authors: Polimeno, L., Margiotta, M., Marangi, L., Lisowsky, T., Azzarone, A., Ierardi, E., Frassanito, M.A., Francavilla, R., Francavilla, A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.04.2000
• Subjects: ALR; Animals; Blotting, Western; Cell Division - drug effects; cell proliferation; DNA Primers - chemistry; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Flow Cytometry; Gene Expression - drug effects; Growth Substances - pharmacology; hepatic IFN-γ; Hepatocytes - cytology; Hepatocytes - drug effects; immunosuppression; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interferon-gamma - pharmacology; Killer Cells, Lymphokine-Activated - metabolism; Liver Regeneration - drug effects; Liver Regeneration - immunology; Male; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial Proteins; mitochondrion; Nuclear Proteins; Proteins; Rats; Rats, Inbred F344; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcription Factors - drug effects; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - drug effects; immunosuppression; cell proliferation; hepatic IFN-γ; ALR; mitochondrion
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/S1590-8658(00)80824-5

Background. We have shown that the administration of exogenous Augmenter of Liver Regeneration protein in intact rats i) regulates mitochondrial gene expression by inducing the transcription and translation of the nuclear-encoded mitochondrial transcription factor A, and ii) inhibits the lytic activity of liver-resident Natural Killer cells. Aims. The present investigation was carried out to study the effect, in intact rats, of exogenous administration of Augmenter of Liver Regeneration protein on Interferon-γ, a cytokine produced by activated Natural Killer cells and known to control the expression of mitochondrial transcription factor A, a nuclear gene responsible for mitochondrial metabolism. Methods. Interferon-γ was measured as messenger RNA in liver-derived mononuclear leukocytes and as protein in liver-derived Natural Killer cells after a single injection of Augmenter of Liver Regeneration protein. Results. The data obtained demonstrate that: i) in intact rats, Augmenter of Liver Regeneration protein administration induces a reduction of Interferon-γ in the liver-resident Natural Killer cells and ii) the administration of Interferon-γ in 70% hepatectomized rats is followed by a significant reduction both of the mitochondrial transcription factor A expression and of liver regeneration. Conclusions. These data demonstrate the pivotal role of Augmenter of Liver Regeneration as Growth Factor and as immunoregulator by controlling, through Interferon-γ levels, the mitochondrial transcription factor A expression and the lytic activity of liver-resident Natural Killer cells.