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 language | English |
|---|---|
| Pages (from-to) | 672-677 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 257 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Apr 21 1999 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - IRF-1 is an essential mediator in IFN-γ-induced cell cycle arrest and apoptosis of primary cultured hepatocytes
AU - Kano, Arihiro
AU - Haruyama, Takahiro
AU - Akaike, Toshihiro
AU - Watanabe, Yoshifumi
PY - 1999/4/21
Y1 - 1999/4/21
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033590929&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1999.0276
DO - 10.1006/bbrc.1999.0276
M3 - Article
C2 - 10208842
AN - SCOPUS:0033590929
VL - 257
SP - 672
EP - 677
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -