Human Gene Set: GSE14769_UNSTIM_VS_360MIN_LPS_BMDM_DN


Standard name GSE14769_UNSTIM_VS_360MIN_LPS_BMDM_DN
Systematic name M3510
Brief description Genes down-regulated in comparison of unstimulated macrophage cells versus macrophage cells stimulated with LPS (TLR4 agonist) for 360 min.
Full description or abstract The innate immune system is a two-edged sword; it is absolutely required for host defense against infection, but if left uncontrolled can trigger a plethora of inflammatory diseases. Here we used systems biology approaches to predict and validate a gene regulatory network involving a dynamic interplay between the transcription factors NF-?B, C/EBP?, and ATF3 that controls inflammatory responses. We mathematically modeled transcriptional regulation of Il6 and Cebpd genes and experimentally validated the prediction that the combination of an initiator (NF-?B), an amplifier (C/EBP?) 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.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 19270711   Authors: Litvak V,Ramsey SA,Rust AG,Zak DE,Kennedy KA,Lampano AE,Nykter M,Shmulevich I,Aderem A
Exact source GSE14769_1135_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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