Figure 6

Optimal modulation of synergism between TRIM4 and TRIM25.
(A) The dose-dependent synergism of the combination of TRIM4 and TRIM25 was evaluated using Bliss combination index. The maximal synergy was achieved in the region of medium doses of TRIM4 and TRIM25. As the dose of TRIMs became high, the pattern switched from synergism to antagonism. (B) Experimental validation of the dose-dependent synergism between TRIM4 and TRIM25. Three sets of luciferase assays evaluated ISRE levels under treatments of single TRIM4, single TRIM25 and combined TRIM4 and TRIM25 at 3 different dosages (low, medium and high). (C–F) Isobologram synergism analysis for TRIM4 and TRIM25 during immune responses. The Loewe Index was used to evaluate the combinatorial effect of TRIM4 and TRIM25. If x% of the isobologram of TRIM4 and TRIM25 (green curve) bowed inward (indicating CILoewe < 1), then the combination of TRIM4 and TRIM25 had synergistic effect. (C) 100%, (D) 90%, (E) 25% and (F) 10% function isobologram analyses were performed.