Granulocyte colony-stimulating factor impairs liver regeneration in mice through the up-regulation of interleukin-1beta.
OBJECTIVE
Stem cell induction via granulocyte colony-stimulating factor (G-CSF) administration is utilized in the treatment of various diseases. Therefore, we examined the effect of G-CSF administration to a liver fibrosis model induced by dimethylnitrosamine (DMN).


METHODS
ICR mice were subcutaneously injected with either G-CSF (150microg/kg) or saline at days 0, 3, 7 and 10. Subacute liver injury was established by intraperitoneal injection of DMN (10mg/kg) on three consecutive days of each week.


RESULTS
G-CSF administration significantly decreased the survival rate of mice treated with DMN. There was no difference in the degree of liver injury or fibrosis between either group of mice. However, assessment by proliferating cell nuclear antigen (PCNA) revealed that the G-CSF-treated mice experienced a greater degree of inhibition of liver cell proliferation than the control mice. Interleukin-1beta (IL-1beta) mRNA expression increased in the livers of G-CSF-treated mice. PCNA staining and analysis of cell cycle-related proteins also revealed that passive immunization with anti-IL-1beta-neutralizing antibody improved the impaired hepatocellular regeneration and resulted in an improved survival rate of mice treated with G-CSF and DMN.


CONCLUSIONS
G-CSF administration suppressed liver cell proliferation through the up-regulation of IL-1beta expression in DMN-induced liver injury.
Ogiso
Tomio
T
Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Nagaki
Masahito
M
Takai
Shinji
S
Tsukada
Yoshihiko
Y
Mukai
Tsuyoshi
T
Kimura
Kiminori
K
Moriwaki
Hisataka
H
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D004128:Dimethylnitrosamine; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D007116:Immunization, Passive; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000401:mortality; D008115:Liver Regeneration / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000032:analysis; D015996:Survival Rate; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
D000906:Antibodies; D053583:Interleukin-1beta; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D004128:Dimethylnitrosamine