Simulation, analysis and validation of intracellular macrophage network model.

<p>Global sensitivity analysis displaying parameter sensitivity ranges on the differentiation of regulatory macrophages (A). Parameters are grouped by associated model species: NFkB-associated (purple), LANCL2-associated (red), PKA-associated (blue), IL10-associated (green). Predicted impairment of regulatory macrophage differentiation following simulated loss of LANCL2 (B). Fold changes in molecule production or activation following simulated loss of LANCL2 compared to wild-type simulation (C). mRNA expression of LANCL2 in whole stomach (D) and cultured bone marrow derived macrophages (E), normalized to expression of beta-actin. mRNA expression of Ncor2 (F) and Foxp1 (G), Klf4 (H), and Il10 (I) within the stomach of <i>H</i>. <i>pylori</i> SS1-infected and uninfected LANCL2fl/fl; LysCre- and LANCL2fl/fl LysCre+ mice at three weeks post-infection. NFkB p65 activity in whole stomach tissue homogenate of <i>H</i>. <i>pylori</i> SS1-infected and uninfected LANCL2fl/fl; LysCre- and LANCL2fl/fl LysCre+ mice at three weeks post-infection (J). <i>p</i>-values less than 0.05 are considered significant and marked by an asterisk (*), (n = 7).