Caspase-1-independent, Fas/Fas ligand-mediated IL-18 secretion from macrophages causes acute liver injury in mice

被引：227

作者：

Tsutsui, H

Kayagaki, N

Kuida, K

Nakano, H

Hayashi, N

Takeda, K

Matsui, K

Kashiwamura, S

Hada, T

Akira, S

Yagita, H

Okamura, H

Nakanishi, K ^{[1
]}

机构：

[1] Hyogo Coll Med, Dept Immunol & Med Zool, Inst Adv Med Sci, Nishinomiya, Hyogo 6638501, Japan

[2] Hyogo Coll Med, Dept Internal Med 3, Inst Adv Med Sci, Nishinomiya, Hyogo 6638501, Japan

[3] Hyogo Coll Med, Host Def Lab, Inst Adv Med Sci, Nishinomiya, Hyogo 6638501, Japan

[4] Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Suita, Osaka 5650871, Japan

[5] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1138421, Japan

[6] Vertex Pharmaceut, Cambridge, MA 02139 USA

[7] Japan Sci & Technol Corp, Tokyo 1010062, Japan

来源：

IMMUNITY | 1999年 / 11卷 / 03期

关键词：

D O I：

10.1016/S1074-7613(00)80111-9

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 IFN gamma-dependent manner, and these macrophages became competent to secrete mature IL-18 upon stimulation with Fast. This was also the case for caspase-1-deficient mice. Administration of recombinant soluble Fast (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 Fast-stimulated macrophages and its critical involvement in Fast-induced liver injury.

引用

页码：359 / 367

页数：9

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[1] Involvement of caspase-1 and caspase-3 in the production and processing of mature human interleukin 18 in monocytic THP.1 cells [J].