Figure 6. Boolean network model reveals signaling dynamics downstream of sCD40L + glutamate treatment of monocytes and predicts c-Myc as a likely regulator of PSGL-1 induction.

The network illustrated in Fig. 4 was implemented in Python using the Boolean net library, with log rules describing the regulatory interaction between nodes inferred based on the literature describing the regulation. A total of 800 simulations, with 80 time steps, of the CD40L + glutamate-alone scenario were run using an asynchronous update schedule. The fraction of simulations in which a node was on or had a value of 1 is shown for selected signaling intermediates in A–D. The difference in the percentage of simulations in which a node was “on” between the combination scenario and CD40L-alone scenario is shown in E–H. A positive value indicates increased activation in the combination scenario. (A and E) The NF-κB family members p52 and p65 are shown. (B and F) The MAPK family members ERK, p38, and JNK are shown. (C and G) The reactive oxygen intermediates O₂ and H₂O₂ are shown. (D and H) The reduced GSH and oxidized GSSG form of GSH are shown. Shown are the dynamics of the transcription factor complexes p50/p65, p52/RelB, cFos/cJun (AP-1), c-Myc/MAX, and MAX/MAX (I) and the change in the steady-state values relative to CD40L alone (J).