| URN | urn:agi-llid:3593 |
|---|---|
| Name | IL12B |
| Description | interleukin 12b |
| Connectivity | 479 |
| Notes | A direct role for IL12B in susceptibility to inflammatory bowel disease is unlikely. A direct role for IL12B in susceptibility to inflammatory bowel disease is unlikely. A key mechanism in the pathogenesis of MS is the increased expression of CD86 and CD40L and the increased production of IL12 during disease progression. ATPgammaS potentiated the IL-12p40 release induced by TNF-alpha. This potentiation was observed as long as the IL-12p40 concentration under agonist stimulation remained below a threshold value close to 10 ng/ml; inhibition was observed above this value. DISCUSSION FORUM: it is the p40 protein, either alone or paired with other polypeptides, rather than p75, that acts as an interface between the innate and adaptive immune responses. Data show that reverse signaling via 4-1BB-ligand enhanced interleukin-12beta mRNA and the secretion of IL-12 p70 in various antigen-presenting cells, including monocytes. Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma in school-age children. Diesel exhaust particles seem to inhibit the production of IL-12 p40 in lipopolysaccharide activated monocytes as a model for lung macrophages. Frequencies of the various genotypes for the promoter region of the gene encoding IL-12p40 (IL12B) did not differ between psoriasis patients and controls. Heparins (unfractionated heparin, UFH and low molecular weight heparin certoparin) had no effect on the release of IL-1ra, IL-10, and IL-12p40 from neutrophils or peripheral blood mononuclear cells. Heterozygosity of a polymorphism in the 3'untranslated region of the IL12B gene was associated with a delayed disease in late-onset diabetics. IL-12 expression in PMN of SLE patients was less prominent than that of the normal controls. IL-12B 3'untranslated region has no effect or has a negligible effect on human susceptibility to tuberculosis. IL12B SNP is associated with susceptibility to atopic dermatitis and psoriasis vulgaris, presumably by affecting the Th1/Th2 balance. IL12B promoter heterozygosity contributes to asthma severity rather than susceptibility per se. Interleukin-10 induction of endothelial nitric-oxide synthase expression attenuates CD40-mediated interleukin-12 synthesis in human endothelial cells. Leishmania priming of human dendritic cells for CD40 ligand-induced interleukin-12p40 secretion is strain and species dependent. No association of IL12B polymorphisms and self-limited HCV infection could be demonstrated. STATE OF ART REVIEW. Malignant B-cells from follicular and marginal zone lymphomas expressed IL-12 p35 and p40 transcripts, whereas only p35 mRNA was detected in mantle cell lymphoma. The IL12B 1188 (A-->C) gene polymorphism is not involved in defining the genetic basis of the susceptibility to and final outcome of peptic ulcer disease. The IL12B TaqI gene polymorphisms do not appear to be involved in susceptibility to celiac disease. The IL12B gene does not confer susceptibility to coeliac disease. The polymorphism of IL12B (1188A/C) appears to have some influence on the outcome of hepatitis c virus infection. The pro-inflammatory nature of hResistin was further evident from the ability of this protein to induce the nuclear translocation of NF-kappaB transcription factor as seen from electrophoretic mobility shift assays. The purified lipoprotein, Lpk, from Mycobacterium leprae, was found to induce production of interleukin-12 in human peripheral blood monocytes. This gene encodes a subunit of interleukin 12, a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. Interleukin 12 is a disulfide-linked heterodimer composed of the 40 kD cytokine receptor like subunit encoded by this gene, and a 35 kD subunit encoded by IL12A. This cytokine is expressed by activated macrophages that serve as an essential inducer of Th1 cells development. This cytokine has been found to be important for sustaining a sufficient number of memory/effector Th1 cells to mediate long-term protection to an intracellular pathogen. Overexpression of this gene was observed in the central nervous system of patients with multiple sclerosis (MS), suggesting a role of this cytokine in the pathogenesis of the disease. The promoter polymorphism of this gene has been reported to be associated with the severity of atopic and non-atopic asthma in children. We found a strong association between the IL12B_4237 and IL12B_6402 polymorphisms and an asthma-severity phenotype in whites. Association between IL12B intron 2 polymorphism and tuberculosis and between specific IL12B haplotypes and TB found in Hong Kong Chinese population. Chronically infected patients were significantly more likely than those with resolved HCV infection to be homozygous for the IL-12B 3'-UTR A allele. Identify erythroid Kruppel-like factor as a transcription factor in macrophages able to regulate IL-12 p40 transcription depending on the cellular activation status. Inherited interleukin-12 deficiency: IL12B genotype and clinical phenotype of 13 patients from six kindreds. Interleukin 12 and interferon gamma are involved in inhibition of cytotrophoblastic cell invasion. Interleukin-12 p40 transcription and NF-kappaB activation are inhibited by nitric oxide in macrophages and dendritic cells. No evidence to support the presence of a heterozygote effect of the IL12B promoter polymorphism on the level of asthma in early childhood or adulthood. P300 is involved in the transcriptional regulation of IL-12 p40, and IL-12 p40 is one of the target genes of p300. Possible role of IL-12 and tissue antioxidants in development and progression of chronic sinusitis. Results suggest that LPS stimulates the pituitary gland directly in vivo to increase IL-12 p40 gene expression. Results suggest that impaired IL-12 production in HIV-infected myeloid cells occurs, in part, via disruption of IL-12 p40 gene expression in a manner that requires cellular infection. Role of CD28 and IL-12/IL-15 signaling impairment in T cell proliferative deficiency during senescence. Study shows that PBMCs of patients with advanced gastric cancer show poor production of TNF and IL-12p40 in response to stimulation with tumor cells in vitro & this unresponsiveness is associated in some patients with diminished IRAK-1 expression in vivo. Synthesis in RAW264.7 cells is induced by IRF-8. |
| KEGG pathway | Type I diabetes mellitus |
|---|---|
| Cytokine-cytokine receptor interaction | |
| Jak-STAT signaling pathway | |
| Toll-like receptor signaling pathway |
| Swiss-Prot Accession | P29460 |
|---|---|
| Q8N0X8 | |
| P43432 | |
| Q3ZAX5 | |
| Q9R278 | |
| Q62712 |
| Unigene ID | Hs.674 |
|---|---|
| Mm.239707 | |
| Rn.48686 |
| KEGG ID | hsa:3593 |
|---|---|
| mmu:16160 | |
| rno:64546 |
| Swiss-Prot ID | IL12B_HUMAN |
|---|---|
| IL12B_MOUSE | |
| Q3ZAX5_MOUSE | |
| Q9R278_RAT |
| Cell Localization | Extracellular |
|---|
| GO ID | 0005125 |
|---|---|
| 0004896 | |
| 0042164 | |
| 0005143 | |
| 0005515 | |
| 0046982 | |
| 0042803 | |
| 0004871 | |
| 0042088 | |
| 0042093 | |
| 0007050 | |
| 0016477 | |
| 0007166 | |
| 0002323 | |
| 0048662 | |
| 0042104 | |
| 0045785 | |
| 0045078 | |
| 0032729 | |
| 0032816 | |
| 0002860 | |
| 0034393 | |
| 0042035 | |
| 0010224 | |
| 0019233 | |
| 0005576 | |
| 0043514 | |
| 0016020 | |
| 0042102 | |
| 0005615 | |
| 0050671 | |
| 0030101 | |
| 0019735 | |
| 0016021 | |
| 0042095 | |
| 0005524 | |
| 0004672 | |
| 0004674 | |
| 0006468 |
| Pathway | IL12R -> NF-kB/NFATC signaling |
|---|---|
| IL12R -> STAT signaling | |
| PPARG Targets | |
| VDR Targets |
| IPI ID | IPI00021798 |
|---|---|
| IPI00120356 | |
| IPI00207823 |
| Ariadne Ontology | Cytokine |
|---|
| Mouse chromosome position | 11 19.0 cM |
|---|
| GO Molecular Function | protein binding |
|---|---|
| cytokine receptor activity | |
| interleukin-12 alpha subunit binding | |
| protein homodimerization activity | |
| protein heterodimerization activity | |
| cytokine activity | |
| interleukin-12 receptor binding | |
| signal transducer activity |
| Homologene ID | 1648 |
|---|
| Hugo ID | 5970 |
|---|
| GO Cellular Component | extracellular region |
|---|---|
| membrane | |
| extracellular space | |
| interleukin-12 complex |
| MGI ID | 96540 |
|---|
| Human chromosome position | 5q31.1-q33.1 |
|---|
| GO Biological Process | positive regulation of cell adhesion |
|---|---|
| negative regulation of smooth muscle cell proliferation | |
| positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target | |
| positive regulation of natural killer cell activation | |
| positive regulation of T cell proliferation | |
| positive regulation of activated T cell proliferation | |
| positive regulation of smooth muscle cell apoptosis | |
| positive regulation of interferon-gamma biosynthetic process | |
| positive regulation of interferon-gamma production | |
| regulation of cytokine biosynthetic process | |
| cell surface receptor linked signal transduction | |
| natural killer cell activation during immune response | |
| T-helper cell differentiation | |
| cell cycle arrest | |
| cell migration | |
| T-helper 1 type immune response | |
| sensory perception of pain | |
| response to UV-B |
| Rat chromosome position | 10q21 |
|---|
| Group | Cytokine |
|---|---|
| extracellular region | |
| membrane | |
| extracellular space | |
| interleukin-12 complex | |
| protein binding | |
| cytokine receptor activity | |
| interleukin-12 alpha subunit binding | |
| protein homodimerization activity | |
| protein heterodimerization activity | |
| cytokine activity | |
| interleukin-12 receptor binding | |
| signal transducer activity | |
| positive regulation of cell adhesion | |
| negative regulation of smooth muscle cell proliferation | |
| positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target | |
| positive regulation of natural killer cell activation | |
| positive regulation of T cell proliferation | |
| positive regulation of activated T cell proliferation | |
| positive regulation of smooth muscle cell apoptosis | |
| positive regulation of interferon-gamma biosynthetic process | |
| positive regulation of interferon-gamma production | |
| regulation of cytokine biosynthetic process | |
| cell surface receptor linked signal transduction | |
| natural killer cell activation during immune response | |
| T-helper cell differentiation | |
| cell cycle arrest | |
| cell migration | |
| T-helper 1 type immune response | |
| sensory perception of pain | |
| response to UV-B |
| RGD ID | 628704 |
|---|---|
| 61304 |
| LocusLink ID | 3593 |
|---|---|
| 16160 | |
| 64546 | |
| 116997 |
| Alias | CLMF |
|---|---|
| NKSF | |
| CLMF2 | |
| NKSF2 | |
| IL-12B | |
| interleukin 12B | |
| IL12, subunit p40 | |
| OTTHUMP00000160820 | |
| interleukin 12, p40 | |
| interleukin-12 beta chain | |
| natural killer cell stimulatory factor, 40 kD subunit | |
| p40 | |
| Il12p40 | |
| Il-12p40 | |
| RP23-388G23.1 | |
| IL-12 p40 | |
| IL-23 subunit p40 | |
| OTTMUSP00000005619 | |
| Il12 | |
| interleukin-12 p40 | |
| Cytotoxic lymphocyte maturating factor 40 kDa subunit | |
| cytotoxic lymphocyte maturating factor 2 | |
| cytotoxic lymphocyte maturating factor II | |
| cytotoxic lymphocyte maturating factor 2, p40 | |
| I12B_MOUSE | |
| Interleukin IL12 beta | |
| Cytotoxic lymphocyte maturation factor 40 kDa subunit | |
| cytotoxic lymphocyte maturation factor 2 | |
| cytotoxic lymphocyte maturation factor 2, p40 | |
| I12B | |
| interkeukin-12 beta chain | |
| Interleukin IL12AB | |
| Interleukin-12 beta | |
| NK cell stimulatory factor chain 2 | |
| I12B_HUMAN | |
| IL23, subuint p | |
| cytotoxic lymphocyte maturation factor 2, p | |
| NK cell stimulatory factor chain II | |
| IL23, subuint p40 | |
| natural killer cell stimulatory factor-2 | |
| cytotoxic lymphocyte maturation factor II | |
| natural killer cell stimulatory factor II | |
| Il12b | |
| bronchial hyperresponsiveness 1 | |
| Bronchial hyperresponsiveness-1 (bronchial asthma) | |
| bronchial hyperresponsiveness I | |
| BHR I | |
| BHR1 | |
| natural killer cell stimulatory factor | |
| IL-12-specific subunit p40 | |
| Interleukin 12 | |
| interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40) | |
| CLMF P40 | |
| subunit p40 | |
| interleukin-12 p40 precursor |
| Organism | Homo sapiens |
|---|---|
| Mus musculus | |
| Rattus norvegicus |
| OMIM ID | 161561 |
|---|---|
| 600807 | |
| 209950 | |
| 177900 |