Time course of bone marrow-derived macrophages simulated with LPS
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-κB, C/EBPδ, 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-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.
keywords: NCBI GEO macrophages expression profiling by array
- Project website
- https://www.ncbi.nlm.nih.gov/bioproject/PRJNA112151
- Start date
- -
- End date
- -
- Funding
- -
- Types
- NCBI GEO
- Project publications
- https://pubmed.ncbi.nlm.nih.gov/19270711