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Caspase-1-Independent, Fas/Fas Ligand–Mediated IL-18 Secretion from Macrophages Causes Acute Liver Injury in Mice

Open access
Tsutsui, Hiroko, Kayagaki, Nobuhiko, Kuida, Keisuke, Nakano, Hiroki, Hayashi, Nobuki, Takeda, Kiyoshi, Matsui, Kiyoshi, Kashiwamura, Shin-Ichiro, Hada, Toshikazu, Akira, Shizuo, Yagita, Hideo, Okamura, Haruki, Nakanishi, Kenji·1999·Immunity

Abstract

IL-18, produced as a biologically inactive precursor, is processed by caspase-1 in LPS-activated macrophages. Here, we investigated caspase-1-independent processing of IL-18 in Fas ligand (FasL)-stimulated macrophages and its involvement in liver injury. Administration of Propionibacterium acnes (P. acnes) upregulated functional Fas expression on macrophages in an IFNgamma-dependent manner, and these macrophages became competent to secrete mature IL-18 upon stimulation with FasL. This was also the case for caspase-1-deficient mice. Administration of recombinant soluble FasL (rFasL) after P. acnes priming induced comparable elevation of serum IL-18 in parallel with elevated serum liver enzyme levels. However, liver injury was not induced in IL-18-deficient mice after rFasL administration. These results indicate a caspase-1-independent pathway of IL-18 secretion from FasL-stimulated macrophages and its critical involvement in FasL-induced liver injury.

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Metadata

Authors
Tsutsui, H., Kayagaki, N., Kuida, K., Nakano, H., Hayashi, N., Takeda, K., Matsui, K., Kashiwamura, S.-I., Hada, T., Akira, S., Yagita, H., Okamura, H., & Nakanishi, K.
Venue
Immunity
Publisher
Elsevier BV
Published
1999-09
Volume
11
Issue
3
Pages
359-367
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2033300203
Cited by
243
References
0
FWCI
5.98
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Caspase-1-Independent, Fas/Fas Ligand–Mediated IL-18 Secretion from Macrophages Causes Acute Liver Injury in Mice. https://app.cochat.ai/papers/10.1016/s1074-7613(00)80111-9
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Tsutsui, H., Kayagaki, N., Kuida, K., Nakano, H., Hayashi, N., Takeda, K., Matsui, K., Kashiwamura, S.-I., Hada, T., Akira, S., Yagita, H., Okamura, H., & Nakanishi, K. (1999). Caspase-1-Independent, Fas/Fas Ligand–Mediated IL-18 Secretion from Macrophages Causes Acute Liver Injury in Mice. Immunity. https://doi.org/10.1016/s1074-7613(00)80111-9

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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