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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)672-677
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume257
Issue number3
DOIs
Publication statusPublished - Apr 21 1999
Externally publishedYes

Fingerprint

Interferon Regulatory Factor-1
Cell Cycle Checkpoints
Hepatocytes
Cells
Apoptosis
Caspases
Caspase 3
Molecules
Caspase 1
Messenger RNA
DNA Fragmentation
Northern Blotting
Chemical activation
DNA

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

IRF-1 is an essential mediator in IFN-γ-induced cell cycle arrest and apoptosis of primary cultured hepatocytes. / Kano, Arihiro; Haruyama, Takahiro; Akaike, Toshihiro; Watanabe, Yoshifumi.

In: Biochemical and Biophysical Research Communications, Vol. 257, No. 3, 21.04.1999, p. 672-677.

Research output: Contribution to journalArticle

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