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


OBJECTIVE
The present investigation was carried out to study the effect, in intact rats, of exogenous administration of Augmenter of Liver Regeneration protein on Interferon-gamma, 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-gamma 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-gamma in the liver-resident Natural Killer cells and ii) the administration of Interferon-gamma 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-gamma levels, the mitochondrial transcription factor A expression and the lytic activity of liver-resident Natural Killer cells.
Polimeno
L
L
Dept. Emergency and Organ Transplantation, University of Bari, Italy.
Margiotta
M
M
Marangi
L
L
Lisowsky
T
T
Azzarone
A
A
Ierardi
E
E
Frassanito
M A
MA
Francavilla
R
R
Francavilla
A
A
D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D050862:Oxidoreductases Acting on Sulfur Group Donors
D017931:DNA Primers; D004268:DNA-Binding Proteins; D006133:Growth Substances; D007371:Interferon-gamma; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C489030:Tfam protein, rat; C088825:GFER protein, rat; D050862:Oxidoreductases Acting on Sulfur Group Donors; C422562:mitochondrial transcription factor A