Induction of IL-1Ra by dsRNA in FLS. The TLR3 is activated by extracellular virus- or host-derived structured RNA by endocytosis. The activated TLR3 recruits WDFY1 and TRIF, which further recruit TRAF3, PI3K, and TRAF6. The TRAF3 and PI3K activates transcription factor IRF3 while the TRAF6 activates the NF-κB, ERK-MSKs, p38 MAPK and JNK pathways though the TAK1 complex. IRF3 and NF-κB induce the expression of anti-proinflammatory cytokine IL-1Ra and type I IFN, while CREB and ATF1 negatively regulate the IL-1Ra and type I IFN production. Simultaneously, the NF-κB and AP-1 induce proinflammatory cytokine production. IL-1Ra, IL-1 receptor antagonist; TLR3, toll-like receptor 3; IRF3, interferon regulatory factor 3.