A mechanistic integrative computational model of macrophage polarization: Implications in human pathophysiology
Fig 2
IFN-γ-mediated signaling controls macrophage phenotype.
In response to different doses of IFN-γ treatment, the model simulations are compared with corresponding literature time-course data including (A) degradation of receptor-bound IFN-γ [59], (B) phosphorylation of receptor-associated JAK [15], (C) phosphorylation of STAT1 [60], (D) expression of IRF-1 [61], (E) expression of iNOS [62], (F) levels of secreted TNFα [17], (G) levels of secreted IL-12 [16], (H) levels of secreted CXCL-9 [16], (I) intracellular mRNA expression of CXCL-10 [63], (K) expression of miR-3473b [42], plus single timepoint measurements including intracellular levels of (J) itaconic acid at 18 h [64], (L) PTEN at 36 h (in response to miR-3473b mimic transfection, see also S2H Fig) [42], and (M) HIF-1α (in response to IFN-γ with or without hypoxia) [48]. (A-M) All literature data are measured in macrophage cell lines and values are for protein levels unless noted otherwise. Y-axes show normalized expression respectively (A-E, G-I, K: simulations and data are normalized to the maximum expression; F, L: normalized to the no-treatment/time 0 expression; J: normalized to the expression at 18 h; M: normalized to the expression under IFN-γ treatment with hypoxia). S–simulation, D–literature data, Utr–untreated, Trd–IFN-γ treated, Hyp–hypoxia.