Protective role of interleukin-18 against Fas-mediated liver injury

Yamamoto,Norihiko; Murata,Kazumoto; Yoneda,Kentaro; Fuke,Hiroyuki; Yamaguchi,Yumi; Ito,Keiichi; Sugimoto,Kazushi; Shiraki,Katsuya; Yamanaka,Kei-ichi; Mizutani,Hitoshi; Takei,Yoshiyuki

doi:10.3892/ijmm.22.1.43

July 2008 Volume 22 Issue 1

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July 2008 Volume 22 Issue 1

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Article

Protective role of interleukin-18 against Fas-mediated liver injury

Authors:
- Norihiko Yamamoto
- Kazumoto Murata
- Kentaro Yoneda
- Hiroyuki Fuke
- Yumi Yamaguchi
- Keiichi Ito
- Kazushi Sugimoto
- Katsuya Shiraki
- Kei-ichi Yamanaka
- Hitoshi Mizutani
- Yoshiyuki Takei
View Affiliations / Copyright

Affiliations: Department of Gastroenterology, Mie University Graduate School of Medicine, Tsu City, Mie Prefecture, Japan
Pages: 43-48
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Published online on: July 1, 2008

https://doi.org/10.3892/ijmm.22.1.43
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Abstract

Interleukin (IL)-18 plays an important role in the pathogenesis of several liver diseases as well as Fas-mediated apoptosis. However, the effects of IL-18 on Fas-mediated liver injury have not been well elucidated. Therefore, we examined the effects of IL-18 on Fas-mediated apoptosis in in vitro and in vivo experiments. We found that recombinant IL-18 protected mouse hepatocellular carcinoma cell lines, BNL5, from Fas-mediated apoptosis in a dose-dependent manner with up-regulation of both nuclear factor (NF) κB and X-linked inhibitors of apoptosis (XIAP). IL-18 transgenic (Tg) mice were also protected from Fas-mediated liver injury and this was further confirmed by histological study and TUNEL staining. In IL-18 Tg mice, up-regulation of XIAP and down-regulation of caspase 3 were observed after injection of anti-Fas, which was consistent with the in vitro findings. These results suggest that IL-18 suppresses Fas-mediated apoptosis of hepatocytes by up-regulation of NFκB and XIAP, following inhibition of caspase-3 activity. This observation raises the possibility that IL-18 could be a therapeutic strategy for Fas-mediated liver injury as a negative regulator of XIAP.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Protective role of interleukin-18 against Fas-mediated liver injury

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Abstract

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