TABLE 4

Predicted upstream regulators of differentially abundant proteins, as determined by Ingenuity's IPA software

Upstream regulatorMolecule typeFunctionActivation Z-scoreaP valuebTarget molecules in data set
IL-6CytokineInducer of the acute-phase response; differentiation of monocytes and lymphocytes; differentiates B cells into Ig-secreting cells2.4564.74E−10CES2, ELANE, GSTA1, ITLN1, LCN2, MPO, NOS2, S100A9, STAT1, STAT3, WARS
IL-12βCytokineExpressed by macrophages, which induce Th1 cell development; helps sustain a sufficient number of memory Th1 cells for long-term protection2.1917.89E−09NOS2, S100A8, S100A9, STAT1, STAT3
IL-17ACytokineProduced by activated T cells, regulates NF-κB and mitogen-activated protein kinases, stimulates IL-6 expression, enhances nitric oxide production2.133.17E−06LCN2, MPO, NOS2, S100A8, S100A9, STAT3
OSMCytokineMember of the IL-6 cytokine family; regulator of IL-6, G-CSF, and GM-CSF from endothelial cellsc2.54.06E−06LCN2, MAOA, NOS2, S100A8, S100A9, STAT1, STAT3
CEBPATranscription regulatorA bZIP transcription factor; binds to CCAAT motifs in promoters/enhancers, modulates gene expression, interacts with some kinases, and arrests growth2.3861.34E−05LCN2, MPO, S100A8, S100A9, CKAP4, ELANE
IFN-α/βCytokineProduced in macrophages in response to infection2.1846.36E−05NOS2, S100A9, STAT1, STAT3, WARS
IFN-γCytokineProduced by antigen-activated lymphocytes; immunoregulatory activities, activator of macrophages, potentiates IFN effects2.7511.48E−04LCN2, NOS2, S100A8, S100A9, STAT1, STAT3, WARS, CAV1
IL-1βCytokineProduced by activated macrophages via caspase-1; mediates the inflammatory response, B-cell maturation, and apoptosis2.375.13E−04LCN2, NOS2, S100A8, S100A9, STAT1, GSTA1
  • a Based on the log2 ratio, P value, and the statistical effect size. All regulators were predicted to be activated.

  • b P values were generated by Fisher's exact t test.

  • c G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor.