TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes

被引：340

作者：

Yarilina, Anna ^{[1
]}

Park-Min, Kyung-Hyun ^{[1
]}

Antoniv, Taras ^{[1
]}

Hu, Xiaoyu ^{[1
]}

Ivashkiv, Lionel B. ^{[1
,2
]}

机构：

[1] Hosp Special Surg, Arthritis & Tissue Degenerat Program, New York, NY 10021 USA

[2] Cornell Univ, Weill Grad Sch Med Sci, Grad Program Immunol & Microbiol Pathogenesis, New York, NY 10021 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 04期

关键词：

D O I：

10.1038/ni1576

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Rapid induction of inflammatory genes by tumor necrosis factor (TNF) has been well studied, but little is known about delayed and chronic TNF responses. Here we investigated the kinetics of primary macrophage responses to TNF and discovered that TNF initiates an interferon-beta-mediated autocrine loop that sustains expression of inflammatory genes and induces delayed expression of interferon-response genes such as those encoding the transcription factors STAT1 and IRF7, which enhance macrophage responses to stimulation of cytokines and Toll-like receptors. TNF-induced interferon-beta production depended on interferon-response factor 1, and downstream gene expression was mediated by synergy between small amounts of interferon-beta and canonical TNF-induced signals. Thus, TNF activates a 'feed-forward' loop that sustains inflammation but avoids the potential toxicity associated with the high interferon production induced by stimulation of Toll-like receptors.

引用

页码：378 / 387

页数：10

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