Figure 9

Simulated time course of the IFN-γ signaling network. (A, B) Macrophages are given 0.15µg/L and 5µg/L IFN-γ treatment for 72 hours, STAT1 responds quickly even at every low concentration while SOCS1 can only be turned on by high dose of IFN-γ; (C) Primed macrophages have an increased pool of STAT1 ready for phosphorylation and activation, while non-primed macrophages still take time to accumulate equal level of STAT1 (D); (D) Increased STAT1 in primed macrophages is rapidly activated by phosphorylation upon the second exposure to high concentration of IFN-γ; on the contrary, single high dose IFN-γ treatment of non-primed cells only initiates a slower and weaker STAT1 phosphorylation (D). The priming effect is also observed when Jak/STAT downstream genes are examined, including IRF-1(E).