Cutting Edge: Synchronization of IRF1, JunB, and C/EBPβ Activities during TLR3-TLR7 Cross-Talk Orchestrates Timely Cytokine Synergy in the Proinflammatory Response.

ABSTRACT: Multiple pathogen-associated molecular pattern-induced TLR pathway cross-talk provokes proinflammatory cytokine synergy in macrophages, which is important for pathogen resistance and immune homeostasis. However, the detailed mechanisms are unclear. In this article, we demonstrate viral RNA analog-induced transcription synergy of Il6 and Il12b via IFN regulatory factor (IRF)1 (TLR3-TIR domain-containing adaptor inducing IFN-β [TRIF] responsive), C/EBPβ (TLR7-MyD88 responsive), and JunB (all responsive). Coactivation of the TLR3 and TLR7 pathways synchronizes the interaction of IRF1, JunB, and C/EBPβ with the Il6 and Il12b promoters, facilitating maximal gene expression. MyD88 pathway activation suppresses TRIF-induced IRF1 in a delayed manner, controlling the magnitude and timing of cytokin

SUBMITTER: Liu Q 

PROVIDER: S-EPMC4505950 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature