Interleukin-12 subunit beta explained
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) 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.
Function
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 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.[1]
Role as IL-23 subunit
Interleukin-12 p40 also serves as a subunit of interleukin 23.[2]
Further reading
- Airoldi I, Guglielmino R, Carra G, Corcione A, Gerosa F, Taborelli G, Trinchieri G, Pistoia V . The interleukin-12 and interleukin-12 receptor system in normal and transformed human B lymphocytes . Haematologica . 87 . 4 . 434–42 . 2002 . 11940489 .
- Abdi K . IL-12: the role of p40 versus p75 . Scand. J. Immunol. . 56 . 1 . 1–11 . 2002 . 12100467 . 10.1046/j.1365-3083.2002.01101.x . 18488948 . free .
- Sieburth D, Jabs EW, Warrington JA, Li X, Lasota J, LaForgia S, Kelleher K, Huebner K, Wasmuth JJ, Wolf SF . Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5 . Genomics . 14 . 1 . 59–62 . 1992 . 1358798 . 10.1016/S0888-7543(05)80283-6 .
- Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Hewick RM . 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 . 1991 . 10.4049/jimmunol.146.9.3074 . 1673147 . 23838991 . free .
- Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, Nabavi N, Wolitzky AG, Quinn PM, Familletti PC . 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 . 1991 . 1674604 . 51614 . 10.1073/pnas.88.10.4143 . 1991PNAS...88.4143G . free .
- Gearing DP, Cosman D . 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 . 1991 . 2070420 . 10.1016/0092-8674(91)90131-H . 41634801 .
- Stern AS, Podlaski FJ, Hulmes JD, Pan YC, Quinn PM, Wolitzky AG, Familletti PC, Stremlo DL, Truitt T, Chizzonite R . 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 . 1990 . 2204066 . 54627 . 10.1073/pnas.87.17.6808 . 1990PNAS...87.6808S . free .
- Aragane Y, Riemann H, Bhardwaj RS, Schwarz A, Sawada Y, Yamada H, Luger TA, Kubin M, Trinchieri G, Schwarz T . IL-12 is expressed and released by human keratinocytes and epidermoid carcinoma cell lines . J. Immunol. . 153 . 12 . 5366–72 . 1995 . 10.4049/jimmunol.153.12.5366 . 7527439 . 36737679 . free .
- Ling P, Gately MK, Gubler U, Stern AS, Lin P, Hollfelder K, Su C, Pan YC, Hakimi J . Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity . J. Immunol. . 154 . 1 . 116–27 . 1995 . 10.4049/jimmunol.154.1.116 . 7527811 . 31733259 . free .
- Murphy TL, Cleveland MG, Kulesza P, Magram J, Murphy KM . Regulation of interleukin 12 p40 expression through an NF-kappa B half-site . Mol. Cell. Biol. . 15 . 10 . 5258–67 . 1995 . 7565674 . 230773 . 10.1128/MCB.15.10.5258.
- Sharma V, Knobloch TJ, Benjamin D . Differential expression of cytokine genes in HIV-1 tat transfected T and B cell lines . Biochem. Biophys. Res. Commun. . 208 . 2 . 704–13 . 1995 . 7695626 . 10.1006/bbrc.1995.1395 .
- Warrington JA, Bengtsson U . 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 . 1995 . 7698768 . 10.1006/geno.1994.1636 .
- D'Andrea A, Ma X, Aste-Amezaga M, Paganin C, Trinchieri G . 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 . 1995 . 7836910 . 2191875 . 10.1084/jem.181.2.537 .
- Gillessen S, Carvajal D, Ling P, Podlaski FJ, Stremlo DL, Familletti PC, Gubler U, Presky DH, Stern AS, Gately MK . Mouse interleukin-12 (IL-12) p40 homodimer: a potent IL-12 antagonist . Eur. J. Immunol. . 25 . 1 . 200–6 . 1995 . 7843232 . 10.1002/eji.1830250133 . 41702014 .
- Radrizzani M, Accornero P, Amidei A, Aiello A, Delia D, Kurrle R, Colombo MP . 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 . 1995 . 7867080 . 10.1006/cimm.1995.1003 .
- Ma X, Chow JM, Gri G, Carra G, Gerosa F, Wolf SF, Dzialo R, Trinchieri G . The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells . J. Exp. Med. . 183 . 1 . 147–57 . 1996 . 8551218 . 2192398 . 10.1084/jem.183.1.147 .
- Fantuzzi L, Gessani S, Borghi P, Varano B, Conti L, Puddu P, Belardelli F . 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 . 1996 . 8648753 . 190299 . 10.1128/JVI.70.6.4121-4124.1996.
- Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G . 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 . 1996 . 8760829 . 2192696 . 10.1084/jem.184.2.747 .
- Kato K, Shimozato O, Hoshi K, Wakimoto H, Hamada H, Yagita H, Okumura K . 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 . 1996 . 8799158 . 38599 . 10.1073/pnas.93.17.9085 . 1996PNAS...93.9085K . free .
- Taoufik Y, Lantz O, Wallon C, Charles A, Dussaix E, Delfraissy JF . Human immunodeficiency virus gp120 inhibits interleukin-12 secretion by human monocytes: an indirect interleukin-10-mediated effect . Blood . 89 . 8 . 2842–8 . 1997 . 9108403 . 10.1182/blood.V89.8.2842. free .
Notes and References
- Web site: 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 . 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 . November 2000 . 11114383 . 10.1016/S1074-7613(00)00070-4 . free .