Table 3A.
Ingenuity Pathway Analysis (IPA) results showed the significant pathways (∣Z score∣> 2) of up-regulated innatomic genes (IGs) in proinflammatory cytokine KO microarray datasets.
| No. | Significant signaling pathways | Tnf-/- (GSE43145) | Tnfr1,2-/- (GSE33253) | Ifng-/- (GSE9892) | Ifngr1-/- (GSE39592) | Il6-/- (GSE63761) | Il17ra-/- (GSE88800) | Il18-/- (GSE64308) |
|---|---|---|---|---|---|---|---|---|
| 1 | Neuroinflammation Signaling Pathway | ↑ | ↑ | ↑ | ↑ | |||
| 2 | Cardiac Hypertrophy Signaling (Enhanced) | ↑ | ↑ | ↑ | ↑ | |||
| 3 | Leukocyte Extravasation Signaling | ↑ | ↑ | ↑ | ↑ | |||
| 4 | Colorectal Cancer Metastasis Signaling | ↑ | ↑ | ↑ | ↑ | |||
| 5 | Dendritic Cell Maturation | ↑ | ↑ | ↑ | ||||
| 6 | B Cell Receptor Signaling | ↑ | ↑ | ↑ | ||||
| 7 | Tec Kinase Signaling | ↑ | ↑ | ↑ | ||||
| 8 | Production of Nitric Oxide and Reactive Oxygen Species in Macrophages | ↑ | ↑ | ↑ | ||||
| 9 | Integrin Signaling | ↑ | ↑ | ↑ | ||||
| 10 | FGF Signaling | ↑ | ↑ | |||||
| 11 | ILK Signaling | ↑ | ↑ | ↑ | ||||
| 12 | PI3K Signaling in B Lymphocytes | ↑ | ↑ | ↑ | ||||
| 13 | PD-1, PD-L1 cancer immunotherapy pathway | ↓ | ↓ | |||||
| 14 | NF-κB Signaling | ↑ | ↑ | |||||
| 15 | Role of NFAT in Regulation of the Immune Response | ↑ | ↑ | |||||
| 16 | Acute Phase Response Signaling | ↑ | ↑ | |||||
| 17 | HMGB1 Signaling | ↑ | ↑ | |||||
| 18 | RANK Signaling in Osteoclasts | ↑ | ↑ | |||||
| 19 | Type II Diabetes Mellitus Signaling | ↑ | ↑ | |||||
| 20 | Adrenomedullin signaling pathway | ↑ | ↑ | |||||
| 21 | LPS-stimulated MAPK Signaling | ↑ | ↑ | |||||
| 22 | NF-κB Activation by Viruses | ↑ | ↑ | |||||
| 23 | Signaling by Rho Family GTPases | ↑ | ↑ | |||||
| 24 | Cholecystokinin/Gastrin-mediated Signaling | ↑ | ↑ | |||||
| 25 | IL-8 Signaling | ↑ | ↑ | |||||
| 26 | PKCθ Signaling in T Lymphocytes | ↑ | ↑ | |||||
| 27 | Toll-like Receptor Signaling | ↑ | ↑ | |||||
| 28 | IL-1 Signaling | ↑ | ↑ | |||||
| 29 | Interferon Signaling | ↑ | ||||||
| 30 | ERK/MAPK Signaling | ↑ | ||||||
| 31 | Mouse Embryonic Stem Cell Pluripotency | ↑ | ||||||
| 32 | Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes | ↑ | ||||||
| 33 | Th2 Pathway | ↑ | ||||||
| 34 | Systemic Lupus Erythematosus In T Cell Signaling Pathway | ↑ | ||||||
| 35 | Endocannabinoid Cancer Inhibition Pathway | ↑ | ||||||
| 36 | NGF Signaling | ↑ | ||||||
| 37 | Cardiac Hypertrophy Signaling | ↑ | ||||||
| 38 | Synaptogenesis Signaling Pathway | ↑ | ||||||
| 39 | Fc Epsilon RI Signaling | ↑ | ||||||
| 40 | CD28 Signaling in T Helper Cells | ↑ | ||||||
| 41 | EGF Signaling | ↑ | ||||||
| 42 | Rac Signaling | ↑ | ||||||
| 43 | PDGF Signaling | ↑ | ||||||
| 44 | iCOS-iCOSL Signaling in T Helper Cells | ↑ | ||||||
| 45 | Pancreatic Adenocarcinoma Signaling | ↑ | ||||||
| 46 | Ephrin Receptor Signaling | ↑ | ||||||
| 47 | Cdc42 Signaling | ↑ | ||||||
| 48 | p70S6K Signaling | ↑ | ||||||
| 49 | Phospholipase C Signaling | ↑ | ||||||
| 50 | Neurotrophin/TRK Signaling | ↑ | ||||||
| 51 | ErbB Signaling | ↑ | ||||||
| 52 | CD27 Signaling in Lymphocytes | ↑ | ||||||
| 53 | Neuregulin Signaling | ↑ | ||||||
| 54 | Endocannabinoid Developing Neuron Pathway | ↑ | ||||||
| 55 | PFKFB4 Signaling Pathway | ↑ | ||||||
| 56 | GNRH Signaling | ↑ | ||||||
| 57 | Glioma Signaling | ↑ | ||||||
| 58 | Melatonin Signaling | ↑ | ||||||
| 59 | Role of NFAT in Cardiac Hypertrophy | ↑ | ||||||
| 60 | Acute Myeloid Leukemia Signaling | ↑ | ||||||
| 61 | Opioid Signaling Pathway | ↑ | ||||||
| 62 | Sphingosine-1-phosphate Signaling | ↑ | ||||||
| 63 | G Beta Gamma Signaling | ↑ | ||||||
| 64 | Gα12/13 Signaling | ↑ | ||||||
| 65 | Gαq Signaling | ↑ | ||||||
| 66 | Wnt/β-catenin Signaling | ↑ | ||||||
| 67 | Thrombin Signaling | ↑ | ||||||
| 68 | TREM1 Signaling | ↑ | ||||||
| 69 | IL-6 Signaling | ↑ | ||||||
| 70 | LXR/RXR Activation | ↓ | ||||||
| 71 | iNOS Signaling | ↑ | ||||||
| 72 | PPAR Signaling | ↑ | ||||||
| 73 | Systemic Lupus Erythematosus In B Cell Signaling Pathway | ↑ | ||||||
| 74 | Type I Diabetes Mellitus Signaling | ↑ | ||||||
| 75 | p38 MAPK Signaling | ↑ | ||||||
| 76 | Antioxidant Action of Vitamin C | ↓ | ||||||
| 77 | MIF Regulation of Innate Immunity | ↑ | ||||||
| 78 | Inflammasome pathway | ↑ | ||||||
| 79 | Osteoarthritis Pathway | ↑ | ||||||
| 80 | STAT3 Pathway | ↑ | ||||||
| 81 | VDR/RXR Activation | ↑ | ||||||
| 82 | Role of IL-17F in Allergic Inflammatory Airway Diseases | ↑ | ||||||
| 83 | FAT10 Cancer Signaling Pathway | ↑ | ||||||
| 84 | Angiopoietin Signaling | ↓ | ||||||
| 85 | T Cell Exhaustion Signaling Pathway | ↑ | ||||||
| 86 | Endothelin-1 Signaling | ↑ |
A total of 11 microarrays about proinflammatory cytokines in Table 2A were analyzed, GSE15750, GSE73875, GSE64309 and GSE64310 were not included because there were no significant (∣Z score∣< 2) pathways in them.
The data showed a total of 28 shared significant signaling pathways of the up-regulated innate immune genes in PCs KO microarrays. 12 cellular immune response signals were activated and PD-1, PD-L1 cancer immunotherapy pathway was suppressed by the up-regulated IGs (marked in bold). And in 58 unique significant signaling pathways, 12 cellular immune response signals (marked in bold) are activated when one proinflammatory cytokine was KO. The detailed IPA results were showed in Table S7 .