Table V.
Erythropoietin (EPO) and Anakinra Ingenuity Canonical Pathway Analysis
| Pathways | p value | Genes |
|---|---|---|
| 24 h post-TBI: EPO | ||
| Circadian rhythm signaling | 9.55E−05 | PER3, ARNTL, CRY1 |
| IL-17A signaling in fibroblasts | 4.07E−03 | JUN, LCN2 |
| IL-6 signaling | 4.17E−03 | IL-18, JUN, A2M |
| IL-12 signaling and production in macrophages | 4.27E−03 | ALOX15, IL18, JUN |
| Glucocorticoid receptor signaling | 4.90E−03 | JUN, DUSP1, CDKN1A, A2M |
| Acute phase response signaling | 1.05E−02 | ALOX15, IL18, JUN |
| Eicosanoid signaling | 1.07E−02 | ALOX15, LTC4S |
| ATM signaling | 1.12E−02 | JUN, CDKN1A |
| RAR activation | 1.12E−02 | CSF2RB, JUN, DUSP1 |
| IL-10 signaling | 1.58E−02 | IL-18, JUN |
| Crosstalk between dendritic cells and natural killer cells | 1.62E−02 | CSF2RB, IL-18 |
| IL-3 signaling | 1.66E−02 | CSF2RB, JUN |
| Leukotriene biosynthesis | 2.57E−02 | LTC4S |
| PPAR signaling | 2.82E−02 | IL-18, JUN |
| GADD45 signaling | 4.79E−02 | CDKN1A |
| Aryl hydrocarbon receptor signaling | 5.01E−02 | JUN, CDKN1A |
| 72 h post-TBI: EPO | ||
| Eicosanoid signaling | 1.62E−03 | ALOX15, PLA2G4A, PLA2G2A, HPGDS, DPEP2 |
| Fc epsilon RI signaling | 5.50E−03 | PLA2G4A, RAC2, GRAP2, FCER1G, MAP2K3, PLA2G2A |
| Phospholipases | 8.71E−03 | HMOX1, PLA2G4A, PLA2G2A, PLA1A |
| Oncostatin M signaling | 1.51E−02 | TIMP3, OSMR, CHI3L1 |
| GADD45 signaling | 2.95E−02 | PCNA, ADD45A |
| Leukocyte extravasation signaling | 5.75E−02 | ITGB2, RAC2, TIMP3, MMP8, CYBB, SELPLG |
| IL-8 signaling | 1.28E−01 | ITGB2, HMOX1, RAC2, CXCR2, CYBB |
| 72 h post-TBI: anakinra | ||
| PXR/RXR activation | 0.0002 | NR1l3, IGFBP1, CYP2B6 |
| GADD45 signaling | 0.0005 | GADD45A, GADD45G |
| VDR/RXR activation | 0.0098 | GADD45A, IGFBP1 |
| Acute phase response signaling | 0.0389 | IL1RN, SOCS2 |
| 7 days post-TBI: EPO | ||
| GADD45 signaling | 6.76E−03 | CDKN1A, CND1 |
| TR/RXR activation | 1.82E−02 | UCP2, CYP7A1, NCOA4 |
Abbreviations: A2M alpha-2-macroglobulin; ALOX15 arachidonate 15-lipoxygenase; ARNTL aryl hydrocarbon receptor nuclear translocator-like; CCND1 cyclin D1; CDKN1A cyclin-dependent kinase inhibitor 1A; CHI3L1 chitinase 3-like 1; CRY1 cryptochrome 1 (photolyase-like); CSF2RB colony stimulating factor 2 receptor, beta, low-affinity; CXCR2 chemokine (C-X-C motif) receptor 2; CYP2B6 cytochrome P450, family 2, subfamily b, polypeptide 3; CYP7A1 cytochrome P450, family 7, subfamily a, polypeptide 1; CYPP cytochrome b-245, beta polypeptide; DUSP1 dual specificity phosphatase 1; DPEP2 dipeptidase 2; FCER1G Fc fragment of IgE, high affinity I, receptor for; gamma polypeptide; GRAP2 GRB2-related adaptor protein 2; GADD45A growth arrest and DNA-damage-inducible, alpha; GADD45G growth arrest and DNA-damage-inducible, gamma; IGFBP1 insulin-like growth factor 2 mRNA binding protein 1; HMOX1 heme oxygenase (decycling) 1; HPGDS hematopoietic prostaglandin D synthase; IL1RN interleukin 1 receptor antagonist; IL-18 interleukin 18, nintegrin, beta 2; JUN Jun oncogene; LCN2 lipocalin 2; LTC4S leukotriene C4 synthase; MAP2K3 mitogen-activated protein kinase kinase 3; MMP8 matrix metallopeptidase 8; NCOA4 nuclear receptor coactivator 4; Nr1i3 nuclear receptor subfamily 1, group I, member 3; OSMR oncostatin M receptor; PER3 period homolog 3; PLA1A phospholipase A1 member A; PLA2G2A phospholipase A2, group IIA; PLA2G4A phospholipase A2, group IVA; RAC2 ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2); SELPLG selectin P ligand; TIMP3 TIMP metallopeptidase inhibitor 3; SOCS2 suppressor of cytokine signaling 2; UCP2 uncoupling protein 2