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- Title
Function of C/EBPδ in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals.
- Authors
Litvak, Vladimir; Ramsey, Stephen A; Rust, Alistair G; Zak, Daniel E; Kennedy, Kathleen A; Lampano, Aaron E; Nykter, Matti; Shmulevich, Ilya; Aderem, Alan
- Abstract
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-κB, C/EBPδ and ATF3 that controls inflammatory responses. We mathematically modeled transcriptional regulation of the genes encoding interleukin 6 and C/EBPδ and experimentally confirmed the prediction that the combination of an initiator (NF-κB), an amplifier (C/EBPδ) 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.
- Publication
Nature Immunology, 2009, Vol 10, Issue 4, p437
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1721