Ogiso Tomio, Nagaki Masahito, Takai Shinji, Tsukada Yoshihiko, Mukai Tsuyoshi, Kimura Kiminori, Moriwaki Hisataka
Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
J Hepatol. 2007 Dec;47(6):816-25. doi: 10.1016/j.jhep.2007.06.017. Epub 2007 Aug 10.
BACKGROUND/AIMS: 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).
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.
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.
G-CSF administration suppressed liver cell proliferation through the up-regulation of IL-1beta expression in DMN-induced liver injury.
背景/目的：通过给予粒细胞集落刺激因子（G-CSF）诱导干细胞已被用于治疗多种疾病。因此，我们研究了给予G-CSF对二甲基亚硝胺（DMN）诱导的肝纤维化模型的影响。
在第0、3、7和10天，给ICR小鼠皮下注射G-CSF（150μg/kg）或生理盐水。通过每周连续三天腹腔注射DMN（10mg/kg）建立亚急性肝损伤模型。
给予G-CSF显著降低了接受DMN治疗的小鼠的存活率。两组小鼠的肝损伤程度或纤维化程度没有差异。然而，通过增殖细胞核抗原（PCNA）评估发现，与对照小鼠相比，接受G-CSF治疗的小鼠肝细胞增殖受到更大程度的抑制。给予G-CSF治疗的小鼠肝脏中白细胞介素-1β（IL-1β）mRNA表达增加。PCNA染色和细胞周期相关蛋白分析还显示，用抗IL-1β中和抗体进行被动免疫可改善受损的肝细胞再生，并提高接受G-CSF和DMN治疗的小鼠的存活率。
在DMN诱导的肝损伤中，给予G-CSF通过上调IL-1β表达抑制肝细胞增殖。
