Systems Approaches to Modeling Chronic Mucosal Inflammation
Figure 5
Effect of EMT on canonical-noncanonical NF-κB pathway coupling. (a) Relative changes in TRAF1, NF-κB2, and TNIP1 mRNA expressed as fold-change measurements in the absence or presence of TGFβ-induced EMT as indicated. Each point is the mean of a duplicate biological experiment, measured with three technical replicates. (b) XChIP experiments of HSAECs in the presence (grey bars) or absence (black bars) of TGFβ-induced EMT. Shown is fold change in the TRAF1 promoter quantified by Q-gPCR relative to unstimulated HSAEC signal in duplicate experiments. (c) Computational simulations of p52 processing as a function of translational delay for TRAF1 and NFκB2. Abbreviations; T.d., translational delay. (A) shows the effect of increasing TRAF1 translational delay on p52 processing time while keeping the translational delay of NFκB2 either at nominal rate (90′) or higher than nominal rate or lower than nominal rate. (B) shows similar effect but for increasing NFκB2 translational delay (x-axis). (C) shows the contour plot of all simulations (D, E) amantadine-treated A549 cells (200 g/mL) were stimulated with poly I:C and TNIP1/Naf1 (D), and IL8 (E) expression was measured by Q-RT-PCR. Data expressed as fold change as compared to untreated cells after normalizing to internal controls, GAPDH. Data analyzed by a 2-way ANOVA with multiple comparisons. Significantly different from amantadine untreated samples: and . Amantadine-treated cells (light bars) showed higher level of noncanonical pathway inhibition compared to untreated cells (dark bars).
