IRF-1 is an essential mediator in IFN-γ-induced cell cycle arrest and apoptosis of primary cultured hepatocytes

Arihiro Kano, Takahiro Haruyama, Toshihiro Akaike, Yoshifumi Watanabe

研究成果: ジャーナルへの寄稿学術誌査読

123 被引用数 (Scopus)


IFN-γ induces cell cycle arrest and p53-independent apoptosis in primary cultured hepatocytes. However, it is not yet understood what molecules regulate the mechanism. We report here that interferon regulatory factor 1 (IRF-1) is an essential molecule in these phenomena. Hepatocytes from IRF-1-deficient mice were completely resistant to IFN-γ in apoptosis indicated by three different hallmarks such as LDH release, DNA fragmentation and the activation of caspase-3 family. Caspase-1 expression was little detected in hepatocytes, and constitutive and IFN-γ-induced mRNA expression of Fas or caspase-3 did not change in between wild type and IRF-1-deficient hepatocytes. Expression of IFN-γ-inducible caspase, caspase-11, did not change either. Thus, it is unlikely that these molecules directly regulate the mechanisms. Interestingly, IRF-1-deficient hepatocytes were also resistant to IFN-γ-induced cell cycle arrest despite IFN-γ-induced cell cycle arrest and apoptosis are regulated by independent pathways. Results by Northern blot analysis showed that IFN-γ-induced but not constitutive p53 mRNA expression was regulated by IRF-1. In fact, IFN-γ did not induce cell cycle arrest in p53-deficient hepatocytes. Taken together, IRF-1 mediates IFN-γ signaling into primary hepatocytes for cell cycle arrest via p53 expression and for apoptosis.

ジャーナルBiochemical and Biophysical Research Communications
出版ステータス出版済み - 4月 21 1999

!!!All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学


「IRF-1 is an essential mediator in IFN-γ-induced cell cycle arrest and apoptosis of primary cultured hepatocytes」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。