Figure 6.

Relationship between NF-κB and TNF Secretion Recapitulated by a Mathematical Model of the Mechanisms Governing NF-κB Activation and TNF Production

(A) A table cross-correlating, qualitatively, nuclear NF-κB activation and TNF secretion. Cells with a NF-κB peak during LPS stimulation greater than baseline NF-κB level by 2 SDs are categorized as NF-κB+. Other cells are categorized as NF-κB−. Cells with a measured TNF peak larger than 5% of maximum measured TNF in the whole population are defined as TNF+; others are categorized as TNF−.

(B) Quantitative cross-correlation (by Pearson coefficient) between the magnitude of observed NF-κB peak values with observed TNF release peaks.

(C) The modified Caldwell et al. (2014) model to simulate LPS pulse induced TNF secretion at the single-cell level. Extrinsic noise was added by sampling key kinetic parameters from gamma distributions as in Cheng et al. (2015).

(D) Model predictions of active TRIF, nuclear NF-κB, and secreted TNF dynamics in 500 single cells, with red lines showing mean behavior. Simulated secretion profiles agree well with the measured single-cell TNF secretion time courses.

(E) The model simulations indicate that, qualitatively, NF-κB positivity (NF-κB+) correlates better to TNF positivity (TNF+) than TRIF positivity (TRIF+). Many cells categorized as TRIF− may produce TNF above the detectable level.

(F) The model simulations indicate that TNF peak magnitude is not quantitatively correlated (by Pearson coefficient) to nuclear NF-κB peak magnitude but is quantitatively correlated to peak TRIF values.