Table III.
IFN-γ-dependent genes inhibited by IL-12 (65 genes)a
| Common Name | GenBank | Map | WT—IL-12- Treated |
GKO—Not Treated |
GKO—IL-12- Treated |
Function |
|---|---|---|---|---|---|---|
| Proliferin (PLF) | AV290437 | 13 | 15.84 | 2.89 | 1.79 | Angiogenic placental hormone |
| Macrophage-inflammatory protein-2 (MIP2) | X53798 | 4q21 | 6.16 | 2.24 | 1.78 | Chemokine |
| Platelet-derived growth factor-inducible KC protein (GRO1) | J04596 | 5 E–F | 4.79 | 4.74 | 1.75 | A secretory protein related to platelet α-granule proteins |
| Adrenomedullin | U77630 | D7Wsu1 3De | 4.79 | 2.06 | 1.51 | Mitogenic, antiapoptosis factor |
| Matrix metalloproteinase 10, stromelysin-2 | Y13185 | 9 | 4.61 | 1.40 | 1.92 | Degradation of extracellular matrix |
| ADAMTS-1, a disintegrin and metalloprotease with thrombospondin motifs | D67076 | 16 C3–C5 | 4.27 | 1.27 | 1.85 | Cleaves versican in the expanded cumulus oocyte complex |
| Carboxypeptidase X2 | AF017639 | 4.17 | 1.29 | 1.77 | Peptidase | |
| IL-1α | M14639 | 2 F | 4.13 | 1.38 | 1.63 | Inflammatory cytokine |
| Amphiregulin | L41352 | 5 | 4.09 | 0.79 | 1.58 | Ligand for EGFR, growth factor |
| Lymphocyte Ag 57, BLNK | AF068182 | d1 | 4.09 | 4.05 | 3.85 | B lymphopoiesis |
| Intracellular calcium-binding protein (MRP14) | M83219 | 3 | 4.02 | 1.27 | 1.52 | Cell adhesion |
| Placental growth factor, Plgf | X80171 | 12 D | 3.36 | 0.80 | 1.51 | Placental growth factor |
| Urate oxidase, Uox | M27695 | 3 | 3.34 | 1.25 | 1.46 | Converts uric acid to allantoin |
| Ornithine decarboxylase antizyme | AV212241 | 10 | 3.26 | 2.67 | 2.36 | Cell growth inhibition |
| Immediate early response 3, gly96 | X67644 | 3.25 | 1.54 | 1.45 | Unknown | |
| Basonuclin | U88064 | Unknown | 3.14 | 0.86 | 1.41 | Cellular proliferation |
| HMGCR | X07888 | 3.04 | 1.35 | 2.17 | Key enzyme for cholesterol synthesis | |
| Cellular retinoic acid binding protein (CRABP) | X15789 | 9 | 3.04 | 1.45 | 1.39 | Regulation of retinoid acid availability for nuclear receptors |
| c-Fos | V00727 | 12 | 2.99 | 0.82 | 1.31 | Oncogene for cellular proliferation |
| IL-1R, type II | X59769 | 1 | 2.91 | 1.14 | 1.28 | Type II IL-1R |
| Growth factor-inducible immediate early gene (3CH134), Ptpn 16 | X61940 | 17 A2-C | 2.87 | 1.16 | 1.26 | Cell adhesion, migration, and proliferation |
| Parathyroid hormone-related peptide gene, PTHRP | M60057 | 6 F–G | 2.86 | 1.81 | 1.22 | Regulates endochondral ossification during skeletal development |
| Wnt-5a | M89798 | 14 | 2.83 | 1.39 | 1.22 | Mammary cell adhesion |
| mts1 | M36579 | 3 | 2.78 | 1.56 | 1.16 | Associated with tumor metastasis |
| Endothelial-specific receptor tyrosine kinase, Tie 2 | X71426 | 4 | 2.74 | 1.31 | 1.15 | Endothelial cell-specific receptor tyrosine kinase involved in angiogenesis |
| Intracellular calcium-binding protein (MRP8) | M83218 | 3 | 2.72 | 0.66 | 1.14 | Cell adhesion |
| Mature T cell proliferation 1 (MTCP1) | U32332 | X | 2.70 | 0.93 | 1.14 | Oncogene |
| Matrix metalloproteinase 13 | X66473 | 11q22.3 | 2.66 | 1.62 | 2.17 | Degradation of extracellular matrix |
| Short stature homeobox 2, OG-12a homeodomian protein | U66918 | 3 E3-F1 | 2.64 | 0.62 | 1.12 | Involved in growth |
| Chemokine orphan receptor 1, RDC1 | AF000236 | 1 | 2.52 | 1.51 | 1.12 | A coreceptor for HIV and SIV |
| Mglap | D00613 | 6 | 2.50 | 1.76 | 1.11 | Regulation of extracellular matrix calcification |
| Endostatin, α1 (XVIII) collagen | L22545 | 10 | 2.46 | 1.31 | 1.10 | Angiogenic factor |
| Invasion-inducing protein (Tiam1) | U05245 | 16 | 2.44 | 1.89 | 1.06 | Invasion-inducing protein |
| Melanoma Ag H52 | D10049 | 2.37 | 1.16 | 1.04 | Encodes the env gene and LTR of endogenous ecotropic murine leukemia provirus of AKV-type | |
| NS1-associated protein 1-like, RRM RNA binding protein GRY-RBP | AF093821 | Unknown | 2.33 | 1.24 | 1.02 | A component of apobec-1 editosome |
| Eps15 | L21768 | 2.33 | 1.00 | 0.99 | EGF receptor pathway substrate involved in mitogenic activity | |
| Heat shock protein, 70 kDa, 3 | M12571 | 17 | 2.32 | 1.81 | 0.97 | Chaperone of proteins exposed to stress |
| IL-1β | M15131 | 2 F | 2.32 | 0.91 | 0.97 | Inflammatory cytokine |
| Granzyme E | M36901 | 14 | 2.31 | 1.11 | 0.94 | Serine protease |
| Bone sialoprotein (IBSP) | L20232 | 5 | 2.27 | 0.61 | 0.92 | Involved in nucleation of hydroxyapatiteduring de novo bone formation |
| Cyclin-dependent kinase 4 | AA791962 | 2.26 | 0.61 | 0.92 | Regulates cell cycle progression through the G1 phase | |
| Connexin (Cx26) | M81445 | 14 D1-E1 | 2.25 | 1.18 | 0.92 | Gap junctional communication |
| Slfn4 | AF099977 | Unknown | 2.23 | 1.63 | 0.89 | Growth regulatory gene that affects thymocyte development |
| Matrix metalloproteinase 3, stromelysin 1 | X66402 | 9 | 2.22 | 0.59 | 0.89 | Degradation of extracellular matrix |
| RIKEN cDNA 1200008D14 gene | AW208938 | 2.17 | 1.22 | 0.88 | Unknown | |
| Keretin 6a, MK6a, mK6a, Krt2–6c, 2310016L08Rik | AB012033 | 15 | 2.16 | 0.85 | 0.86 | Structural protein of epithelial cells |
| Retinoblastoma susceptibility protein (pp105 Rb) | M26391 | 13q14.2 | 2.15 | 0.64 | 0.83 | Antiapoptotic |
| Cyclin 1 | AF005886 | 5 E3.3-F1.3 | 2.15 | 1.52 | 2.16 | Cell cycle progression |
| Plasminogen activator inhibitor 2 | X16490 | 1 | 2.14 | 0.74 | 0.82 | Cell invasion |
| Adenylate kinase 3 | AB020239 | 4 | 2.10 | 0.81 | 0.81 | Metabolism of ATP |
| Transcription factor AP-2 | U17291 | 13 A5-B1 | 2.10 | 0.94 | 0.81 | Oncogenic transcription factor |
| Early growth response 2 | AV232606 | 10 | 2.10 | 0.75 | 0.81 | Candidate gene for the regulation of pattern formation in the hindbrain |
| Matrilin 2 | U69262 | 2.09 | 1.28 | 0.78 | Component of extracellular filamentous networks | |
| Histone H1 | X72805 | 13 | 2.07 | 1.11 | 0.78 | Nuclear protein |
| Connexin 43 (α1 gap junction) | M63801 | 10 | 2.07 | 1.97 | 0.73 | Gap junctional communication |
| Smooth muscle γ actin gene | U20365 | 6 | 2.06 | 0.76 | 0.71 | Cell structural protein |
| Matrix metalloproteinase 9 | AV239570 | 2 | 2.05 | 0.78 | 0.69 | Degradation of extracellular matrix |
| Hyaluronan synthase 2 | U52524 | c-myc/Dhfr-rs1 | 2.04 | 1.17 | 0.63 | Membrane-bound enzyme for the polymerization of hyaluronan |
| Mast cell protease 8 | X78545 | Unknown | 2.04 | 0.84 | 0.61 | Granule constituent protease |
| Similar to latent TGF-β binding protein-4. | AA838868 | 2.03 | 0.72 | 0.59 | Unknown | |
| Ephrin-A1; ligand for Eph-related receptor tyrosine kinases | U90662 | 3 | 2.02 | 0.65 | 0.57 | Involved in cell migration and adhesion |
| Forkhead box C1 | AF045017 | D13Mit3/D13Bir9 | 2.02 | 1.45 | 2.04 | A TGFβ1-responsive gene |
| ATP-binding cassette, subfamily B (MDR/TAP), member 4 | M24417 | 5 | 2.01 | 1.55 | 0.53 | Compensatory transporter for vincristine and etoposide |
| Tm4sf, Tspan6, TSPAN-6, transmembrane 4 superfamily | AF053454 | 2.01 | 0.35 | 0.51 | Cell motility and metastasis | |
| Viral envelope like protein (G7e) | U69488 | 18.96–18.98 | 2.01 | 0.70 | 0.49 | Unknown (absent in human) |
a
Genes are selected based on the following criteria: 1) they must be expressed two times less than the controls (untreated wild type or GKO) to qualify as IL-12-inhibited genes; 2) their expression detection must be statistically valid as present with detection p < 0.05; 3) IFN-γ-dependent genes are defined as those whose expression must be inhibited by IL-12 in GKO mice less than two times compared with untreated GKO mice; and 4) IFN-γ-independent genes are defined as those whose expression must be inhibited by IL-12 in GKO mice greater than two times compared with untreated GKO mice. GenBank accession numbers are given. Chromosomal locations (map) are given when they are known. The numbers in columns 4–6 are relative fold of expression over the baseline (control untreated, wild-type group), which is arbitrarily set as 1. These numbers are negative, meaning that they represent the degree of inhibition of the expression of these genes by the IL-12 treatment, compared with the baseline.