Human Gene Set: GSE14769_UNSTIM_VS_80MIN_LPS_BMDM_UP
Standard name
GSE14769_UNSTIM_VS_80MIN_LPS_BMDM_UP
Systematic name
M3500
Brief description
Genes up-regulated in comparison of unstimulated macrophage cells versus macrophage cells stimulated with LPS (TLR4 agonist) for 80 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.
