Function of C/EBPδ in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals

被引：235

作者：

Litvak, Vladimir ^{[1
]}

Ramsey, Stephen A. ^{[1
]}

Rust, Alistair G. ^{[1
]}

Zak, Daniel E. ^{[1
]}

Kennedy, Kathleen A. ^{[1
]}

Lampano, Aaron E. ^{[1
]}

Nykter, Matti ^{[1
]}

Shmulevich, Ilya ^{[1
]}

Aderem, Alan ^{[1
]}

机构：

[1] Inst Syst Biol, Seattle, WA USA

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 04期

基金：

美国国家卫生研究院;

关键词：

TOLL-LIKE RECEPTORS; BINDING PROTEIN FAMILY; INNATE IMMUNE-RESPONSE; SYSTEMS BIOLOGY; KAPPA-B; PATHOGEN RECOGNITION; TRANSCRIPTION FACTOR; NEGATIVE REGULATION; GENE-EXPRESSION; ACTIVATION;

D O I：

10.1038/ni.1721

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The innate immune system is like a double-edged sword: it is absolutely required for host defense against infection, but when uncontrolled, it can trigger a plethora of inflammatory diseases. Here we use systems- biology approaches to predict and confirm the existence of a gene- regulatory network involving dynamic interaction among the transcription factors NF-kappa B, C/EBP Omega and ATF3 that controls inflammatory responses. We mathematically modeled transcriptional regulation of the genes encoding interleukin 6 and C/EBP delta and experimentally confirmed the prediction that the combination of an initiator (NF-kappa B), an amplifier (C/EBP delta) and an attenuator (ATF3) forms a regulatory circuit that discriminates between transient and persistent Toll-like receptor 4-induced signals. Our results suggest a mechanism that enables the innate immune system to detect the duration of infection and to respond appropriately.

引用

页码：437 / 443

页数：7

共 37 条

[1] Toll-like receptors in the induction of the innate immune response [J].