Effective COX2 induction depends on the positive feedback between poly-I:C–induced NFκB activation and endogenous TNFα. A, Effective TNFα induction in human macrophages exposed to poly-I:C (pIC) but not rintatolimod (RINT; n = 6). B, Poly-I:C–induced expression of TNFα and COX2 (as well as COX2–dependent suppressive factors CCL22 and IL10) is suppressed by NFκB inhibitor BAY11–7082 (NFκB-I) or TNF receptor inhibitor TNFαRI (TNFα-I) in poly-I:C–stimulated human macrophages (n = 6; mRNA levels, normalized for HPRT). C, Poly-I:C triggers IκB degradation (30 minutes and 1 hours) in macrophages, whereas the TNFα-induced degradation is faster and is compensated already at 1 hour. Note that the IκB degradation triggered by Poly-I:C cannot be prevented by TNRαRI. Results are mean ± SEM. *, P < 0.05 (Wilcoxon signed-rank test).