Subunit beta of interleukin 12 (also known as IL-12B, natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor p40, or interleukin-12 subunit p40)[5] is a protein subunit that in humans is encoded by the IL12Bgene. IL-12B is a common subunit of interleukin 12 and interleukin 23.
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 kDacytokine receptor like subunit encoded by this gene, and a 35 kDa 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.[5]
^Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (November 2000). "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12". Immunity. 13 (5): 715–25. doi:10.1016/S1074-7613(00)00070-4. PMID 11114383.
Further readingedit
Airoldi I, Guglielmino R, Carra G, Corcione A, Gerosa F, Taborelli G, Trinchieri G, Pistoia V (2002). "The interleukin-12 and interleukin-12 receptor system in normal and transformed human B lymphocytes". Haematologica. 87 (4): 434–42. PMID 11940489.
Abdi K (2002). "IL-12: the role of p40 versus p75". Scand. J. Immunol. 56 (1): 1–11. doi:10.1046/j.1365-3083.2002.01101.x. PMID 12100467. S2CID 18488948.
Sieburth D, Jabs EW, Warrington JA, Li X, Lasota J, LaForgia S, Kelleher K, Huebner K, Wasmuth JJ, Wolf SF (1992). "Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5". Genomics. 14 (1): 59–62. doi:10.1016/S0888-7543(05)80283-6. PMID 1358798.
Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Hewick RM (1991). "Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells". J. Immunol. 146 (9): 3074–81. doi:10.4049/jimmunol.146.9.3074. PMID 1673147. S2CID 23838991.
Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, Nabavi N, Wolitzky AG, Quinn PM, Familletti PC (1991). "Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor". Proc. Natl. Acad. Sci. U.S.A. 88 (10): 4143–7. Bibcode:1991PNAS...88.4143G. doi:10.1073/pnas.88.10.4143. PMC51614. PMID 1674604.
Gearing DP, Cosman D (1991). "Homology of the p40 subunit of natural killer cell stimulatory factor (NKSF) with the extracellular domain of the interleukin-6 receptor". Cell. 66 (1): 9–10. doi:10.1016/0092-8674(91)90131-H. PMID 2070420. S2CID 41634801.
Stern AS, Podlaski FJ, Hulmes JD, Pan YC, Quinn PM, Wolitzky AG, Familletti PC, Stremlo DL, Truitt T, Chizzonite R (1990). "Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells". Proc. Natl. Acad. Sci. U.S.A. 87 (17): 6808–12. Bibcode:1990PNAS...87.6808S. doi:10.1073/pnas.87.17.6808. PMC54627. PMID 2204066.
Aragane Y, Riemann H, Bhardwaj RS, Schwarz A, Sawada Y, Yamada H, Luger TA, Kubin M, Trinchieri G, Schwarz T (1995). "IL-12 is expressed and released by human keratinocytes and epidermoid carcinoma cell lines". J. Immunol. 153 (12): 5366–72. doi:10.4049/jimmunol.153.12.5366. PMID 7527439. S2CID 36737679.
Ling P, Gately MK, Gubler U, Stern AS, Lin P, Hollfelder K, Su C, Pan YC, Hakimi J (1995). "Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity". J. Immunol. 154 (1): 116–27. doi:10.4049/jimmunol.154.1.116. PMID 7527811. S2CID 31733259.
Murphy TL, Cleveland MG, Kulesza P, Magram J, Murphy KM (1995). "Regulation of interleukin 12 p40 expression through an NF-kappa B half-site". Mol. Cell. Biol. 15 (10): 5258–67. doi:10.1128/MCB.15.10.5258. PMC230773. PMID 7565674.
Sharma V, Knobloch TJ, Benjamin D (1995). "Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines". Biochem. Biophys. Res. Commun. 208 (2): 704–13. doi:10.1006/bbrc.1995.1395. PMID 7695626.
Warrington JA, Bengtsson U (1995). "High-resolution physical mapping of human 5q31-q33 using three methods: radiation hybrid mapping, interphase fluorescence in situ hybridization, and pulsed-field gel electrophoresis". Genomics. 24 (2): 395–8. doi:10.1006/geno.1994.1636. PMID 7698768.
D'Andrea A, Ma X, Aste-Amezaga M, Paganin C, Trinchieri G (1995). "Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: priming for IL-12 and tumor necrosis factor alpha production". J. Exp. Med. 181 (2): 537–46. doi:10.1084/jem.181.2.537. PMC2191875. PMID 7836910.
Radrizzani M, Accornero P, Amidei A, Aiello A, Delia D, Kurrle R, Colombo MP (1995). "IL-12 inhibits apoptosis induced in a human Th1 clone by gp120/CD4 cross-linking and CD3/TCR activation or by IL-2 deprivation". Cell. Immunol. 161 (1): 14–21. doi:10.1006/cimm.1995.1003. PMID 7867080.
Ma X, Chow JM, Gri G, Carra G, Gerosa F, Wolf SF, Dzialo R, Trinchieri G (1996). "The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells". J. Exp. Med. 183 (1): 147–57. doi:10.1084/jem.183.1.147. PMC2192398. PMID 8551218.
Fantuzzi L, Gessani S, Borghi P, Varano B, Conti L, Puddu P, Belardelli F (1996). "Induction of interleukin-12 (IL-12) by recombinant glycoprotein gp120 of human immunodeficiency virus type 1 in human monocytes/macrophages: requirement of gamma interferon for IL-12 secretion". J. Virol. 70 (6): 4121–4. doi:10.1128/JVI.70.6.4121-4124.1996. PMC190299. PMID 8648753.
Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G (1996). "Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation". J. Exp. Med. 184 (2): 747–52. doi:10.1084/jem.184.2.747. PMC2192696. PMID 8760829.
Kato K, Shimozato O, Hoshi K, Wakimoto H, Hamada H, Yagita H, Okumura K (1996). "Local production of the p40 subunit of interleukin 12 suppresses T-helper 1-mediated immune responses and prevents allogeneic myoblast rejection". Proc. Natl. Acad. Sci. U.S.A. 93 (17): 9085–9. Bibcode:1996PNAS...93.9085K. doi:10.1073/pnas.93.17.9085. PMC38599. PMID 8799158.
Taoufik Y, Lantz O, Wallon C, Charles A, Dussaix E, Delfraissy JF (1997). "Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect". Blood. 89 (8): 2842–8. doi:10.1182/blood.V89.8.2842. PMID 9108403.
January 01, 1970
interleukin, subunit, beta, subunit, beta, interleukin, also, known, natural, killer, cell, stimulatory, factor, cytotoxic, lymphocyte, maturation, factor, interleukin, subunit, protein, subunit, that, humans, encoded, il12b, gene, common, subunit, interleukin. Subunit beta of interleukin 12 also known as IL 12B natural killer cell stimulatory factor 2 cytotoxic lymphocyte maturation factor p40 or interleukin 12 subunit p40 5 is a protein subunit that in humans is encoded by the IL12B gene IL 12B is a common subunit of interleukin 12 and interleukin 23 IL12BAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes1F42 1F45 3D85 3D87 3DUH 3HMX 3QWR 4GRW 4OE8 4OG9IdentifiersAliasesIL12B CLMF CLMF2 IL 12B IMD28 NKSF NKSF2 IMD29 Interleukin 12 subunit beta interleukin 12BExternal IDsOMIM 161561 MGI 96540 HomoloGene 1648 GeneCards IL12BGene location Human Chr Chromosome 5 human 1 Band5q33 3Start159 314 780 bp 1 End159 330 863 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 B1 1 11 25 94 cMStart44 290 890 bp 2 End44 304 860 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inlymph nodepituitary glandappendixtibialis anterior muscleanterior pituitaryrectumgallbladderkidneyrenal cortexlower respiratory tractTop expressed inthymustracheobronchial treespleentracheacarotid bodysubmandibular glandMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functioncytokine activity interleukin 23 receptor binding protein homodimerization activity interleukin 12 receptor binding protein binding identical protein binding protein heterodimerization activity interleukin 12 alpha subunit binding cytokine receptor activity growth factor activity cytokine receptor binding cytokine bindingCellular componentcytoplasm membrane interleukin 12 complex interleukin 23 complex extracellular region extracellular space endoplasmic reticulum lumen cytosol late endosome lumen cell surface external side of plasma membrane receptor complexBiological processpositive regulation of cell adhesion negative regulation of interleukin 10 production negative regulation of smooth muscle cell proliferation positive regulation of inflammatory response sexual reproduction positive regulation of interleukin 12 production positive regulation of smooth muscle cell apoptotic process defense response to Gram negative bacterium positive regulation of interleukin 10 production positive regulation of T cell mediated cytotoxicity natural killer cell activation positive regulation of natural killer cell activation positive regulation of interferon gamma production positive regulation of osteoclast differentiation positive regulation of T helper 17 cell lineage commitment response to organic substance positive regulation of NK T cell activation positive regulation of natural killer cell proliferation natural killer cell activation involved in immune response cell surface receptor signaling pathway positive regulation of NK T cell proliferation positive regulation of T helper 17 type immune response negative regulation of inflammatory response to antigenic stimulus defense response to virus positive regulation of tissue remodeling positive regulation of T helper 1 type immune response positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target positive regulation of granulocyte macrophage colony stimulating factor production positive regulation of T cell proliferation positive regulation of memory T cell differentiation cellular response to interferon gamma positive regulation of tumor necrosis factor production T helper 1 type immune response sensory perception of pain response to UV B positive regulation of interleukin 17 production cellular response to lipopolysaccharide negative regulation of interleukin 17 production T helper cell differentiation cell migration positive regulation of lymphocyte proliferation positive regulation of mononuclear cell proliferation positive regulation of activated T cell proliferation defense response to protozoan positive regulation of defense response to virus by host positive regulation of activation of Janus kinase activity regulation of tyrosine phosphorylation of STAT protein positive regulation of tyrosine phosphorylation of STAT protein interleukin 12 mediated signaling pathway cell population proliferation regulation of signaling receptor activity T helper 1 cell cytokine production cytokine mediated signaling pathway interleukin 23 mediated signaling pathway positive regulation of NIK NF kappaB signalingSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez359316160EnsemblENSG00000113302ENSMUSG00000004296UniProtP29460P43432RefSeq mRNA NM 002187NM 008352NM 001303244RefSeq protein NP 002178NP 001290173Location UCSC Chr 5 159 31 159 33 MbChr 11 44 29 44 3 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 1 1 Role as IL 23 subunit 2 References 3 Further readingFunction editThis 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 kDa cytokine receptor like subunit encoded by this gene and a 35 kDa 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 5 Role as IL 23 subunit edit Interleukin 12 p40 also serves as a subunit of interleukin 23 6 References edit a b c GRCh38 Ensembl release 89 ENSG00000113302 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000004296 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene IL12B interleukin 12B natural killer cell stimulatory factor 2 cytotoxic lymphocyte maturation factor 2 p40 Oppmann B Lesley R Blom B Timans JC Xu Y Hunte B Vega F Yu N Wang J Singh K Zonin F Vaisberg E Churakova T Liu M Gorman D Wagner J Zurawski S Liu Y Abrams JS Moore KW Rennick D de Waal Malefyt R Hannum C Bazan JF Kastelein RA November 2000 Novel p19 protein engages IL 12p40 to form a cytokine IL 23 with biological activities similar as well as distinct from IL 12 Immunity 13 5 715 25 doi 10 1016 S1074 7613 00 00070 4 PMID 11114383 Further reading editAiroldi I Guglielmino R Carra G Corcione A Gerosa F Taborelli G Trinchieri G Pistoia V 2002 The interleukin 12 and interleukin 12 receptor system in normal and transformed human B lymphocytes Haematologica 87 4 434 42 PMID 11940489 Abdi K 2002 IL 12 the role of p40 versus p75 Scand J Immunol 56 1 1 11 doi 10 1046 j 1365 3083 2002 01101 x PMID 12100467 S2CID 18488948 Sieburth D Jabs EW Warrington JA Li X Lasota J LaForgia S Kelleher K Huebner K Wasmuth JJ Wolf SF 1992 Assignment of genes encoding a unique cytokine IL12 composed of two unrelated subunits to chromosomes 3 and 5 Genomics 14 1 59 62 doi 10 1016 S0888 7543 05 80283 6 PMID 1358798 Wolf SF Temple PA Kobayashi M Young D Dicig M Lowe L Dzialo R Fitz L Ferenz C Hewick RM 1991 Cloning of cDNA for natural killer cell stimulatory factor a heterodimeric cytokine with multiple biologic effects on T and natural killer cells J Immunol 146 9 3074 81 doi 10 4049 jimmunol 146 9 3074 PMID 1673147 S2CID 23838991 Gubler U Chua AO Schoenhaut DS Dwyer CM McComas W Motyka R Nabavi N Wolitzky AG Quinn PM Familletti PC 1991 Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor Proc Natl Acad Sci U S A 88 10 4143 7 Bibcode 1991PNAS 88 4143G doi 10 1073 pnas 88 10 4143 PMC 51614 PMID 1674604 Gearing DP Cosman D 1991 Homology of the p40 subunit of natural killer cell stimulatory factor NKSF with the extracellular domain of the interleukin 6 receptor Cell 66 1 9 10 doi 10 1016 0092 8674 91 90131 H PMID 2070420 S2CID 41634801 Stern AS Podlaski FJ Hulmes JD Pan YC Quinn PM Wolitzky AG Familletti PC Stremlo DL Truitt T Chizzonite R 1990 Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B lymphoblastoid cells Proc Natl Acad Sci U S A 87 17 6808 12 Bibcode 1990PNAS 87 6808S doi 10 1073 pnas 87 17 6808 PMC 54627 PMID 2204066 Aragane Y Riemann H Bhardwaj RS Schwarz A Sawada Y Yamada H Luger TA Kubin M Trinchieri G Schwarz T 1995 IL 12 is expressed and released by human keratinocytes and epidermoid carcinoma cell lines J Immunol 153 12 5366 72 doi 10 4049 jimmunol 153 12 5366 PMID 7527439 S2CID 36737679 Ling P Gately MK Gubler U Stern AS Lin P Hollfelder K Su C Pan YC Hakimi J 1995 Human IL 12 p40 homodimer binds to the IL 12 receptor but does not mediate biologic activity J Immunol 154 1 116 27 doi 10 4049 jimmunol 154 1 116 PMID 7527811 S2CID 31733259 Murphy TL Cleveland MG Kulesza P Magram J Murphy KM 1995 Regulation of interleukin 12 p40 expression through an NF kappa B half site Mol Cell Biol 15 10 5258 67 doi 10 1128 MCB 15 10 5258 PMC 230773 PMID 7565674 Sharma V Knobloch TJ Benjamin D 1995 Differential expression of cytokine genes in HIV 1 tat transfected T and B cell lines Biochem Biophys Res Commun 208 2 704 13 doi 10 1006 bbrc 1995 1395 PMID 7695626 Warrington JA Bengtsson U 1995 High resolution physical mapping of human 5q31 q33 using three methods radiation hybrid mapping interphase fluorescence in situ hybridization and pulsed field gel electrophoresis Genomics 24 2 395 8 doi 10 1006 geno 1994 1636 PMID 7698768 D Andrea A Ma X Aste Amezaga M Paganin C Trinchieri G 1995 Stimulatory and inhibitory effects of interleukin IL 4 and IL 13 on the production of cytokines by human peripheral blood mononuclear cells priming for IL 12 and tumor necrosis factor alpha production J Exp Med 181 2 537 46 doi 10 1084 jem 181 2 537 PMC 2191875 PMID 7836910 Gillessen S Carvajal D Ling P Podlaski FJ Stremlo DL Familletti PC Gubler U Presky DH Stern AS Gately MK 1995 Mouse interleukin 12 IL 12 p40 homodimer a potent IL 12 antagonist Eur J Immunol 25 1 200 6 doi 10 1002 eji 1830250133 PMID 7843232 S2CID 41702014 Radrizzani M Accornero P Amidei A Aiello A Delia D Kurrle R Colombo MP 1995 IL 12 inhibits apoptosis induced in a human Th1 clone by gp120 CD4 cross linking and CD3 TCR activation or by IL 2 deprivation Cell Immunol 161 1 14 21 doi 10 1006 cimm 1995 1003 PMID 7867080 Ma X Chow JM Gri G Carra G Gerosa F Wolf SF Dzialo R Trinchieri G 1996 The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells J Exp Med 183 1 147 57 doi 10 1084 jem 183 1 147 PMC 2192398 PMID 8551218 Fantuzzi L Gessani S Borghi P Varano B Conti L Puddu P Belardelli F 1996 Induction of interleukin 12 IL 12 by recombinant glycoprotein gp120 of human immunodeficiency virus type 1 in human monocytes macrophages requirement of gamma interferon for IL 12 secretion J Virol 70 6 4121 4 doi 10 1128 JVI 70 6 4121 4124 1996 PMC 190299 PMID 8648753 Cella M Scheidegger D Palmer Lehmann K Lane P Lanzavecchia A Alber G 1996 Ligation of CD40 on dendritic cells triggers production of high levels of interleukin 12 and enhances T cell stimulatory capacity T T help via APC activation J Exp Med 184 2 747 52 doi 10 1084 jem 184 2 747 PMC 2192696 PMID 8760829 Kato K Shimozato O Hoshi K Wakimoto H Hamada H Yagita H Okumura K 1996 Local production of the p40 subunit of interleukin 12 suppresses T helper 1 mediated immune responses and prevents allogeneic myoblast rejection Proc Natl Acad Sci U S A 93 17 9085 9 Bibcode 1996PNAS 93 9085K doi 10 1073 pnas 93 17 9085 PMC 38599 PMID 8799158 Taoufik Y Lantz O Wallon C Charles A Dussaix E Delfraissy JF 1997 Human immunodeficiency virus gp120 inhibits interleukin 12 secretion by human monocytes an indirect interleukin 10 mediated effect Blood 89 8 2842 8 doi 10 1182 blood V89 8 2842 PMID 9108403 Retrieved from https en wikipedia org w index php title Interleukin 12 subunit beta amp oldid 1170090343, wikipedia, wiki, book, books, library,
