IL-12

Summary

Gene Symbol: IL-12
Description: interleukin 12A
Alias: CLMF, IL-12A, NFSK, NKSF1, P35, interleukin-12 subunit alpha, CLMF p35, IL-12, subunit p35, IL35 subunit, NF cell stimulatory factor chain 1, NK cell stimulatory factor chain 1, cytotoxic lymphocyte maturation factor 1, p35, cytotoxic lymphocyte maturation factor 35 kDa subunit, interleukin 12, p35, interleukin 12A (natural killer cell stimulatory factor 1, cytotoxic lymphocyte maturation factor 1, p35), interleukin-12 alpha chain
Species: human
Products:     IL-12

Top Publications

  1. Tassi E, Braga M, Longhi R, Gavazzi F, Parmiani G, Di Carlo V, et al. Non-redundant role for IL-12 and IL-27 in modulating Th2 polarization of carcinoembryonic antigen specific CD4 T cells from pancreatic cancer patients. PLoS ONE. 2009;4:e7234 pubmed publisher
    ..Hence, loco-regional cytokines delivery or targeted therapy based on antibodies or molecules directed to the tumor stroma might improve anti-tumor immunity and ameliorate fibrosis, without systemic toxicity. ..
  2. Hunt K, Zhernakova A, Turner G, Heap G, Franke L, Bruinenberg M, et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat Genet. 2008;40:395-402 pubmed publisher
    ..Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways. ..
  3. Yilmaz V, Yentür S, Saruhan Direskeneli G. IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine. 2005;30:188-94 pubmed
    ..IL10 proximal and distal promoter SNP distribution with estimated haplotype variations has implicated considerable similarities with the Caucasian populations in Turkey. ..
  4. Oppmann B, Lesley R, Blom B, Timans J, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715-25 pubmed
    A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12...
  5. Hayes M, Wang J, Norcross M. Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes. Blood. 1995;86:646-50 pubmed
    ..stimulus for LPS-induced tumor necrosis factor (TNF) and IL-12 p40 mRNA, but primed poorly for LPS-inducible p35 message and secreted IL-12 activity...
  6. Devergne O, Birkenbach M, Kieff E. Epstein-Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin. Proc Natl Acad Sci U S A. 1997;94:12041-6 pubmed
    ..from lysates and culture media of cells transfected with expression vectors for EBI3 and/or the p35 subunit of IL-12 now reveal a specific association of EBI3 with p35...
  7. D ANDREA A, Rengaraju M, Valiante N, Chehimi J, Kubin M, Aste M, et al. Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J Exp Med. 1992;176:1387-98 pubmed
    ..or interleukin 12 (IL-12), is a 70-kD heterodimeric cytokine composed of two covalently linked chains, p40 and p35. NKSF/IL-12 has multiple effects on T and NK cells and was originally identified and purified from the supernatant ..
  8. Seyerl M, Kirchberger S, Majdic O, Seipelt J, Jindra C, Schrauf C, et al. Human rhinoviruses induce IL-35-producing Treg via induction of B7-H1 (CD274) and sialoadhesin (CD169) on DC. Eur J Immunol. 2010;40:321-9 pubmed publisher
    IL-35 is a heterodimer of EBV-induced gene 3 and of the p35 subunit of IL-12, and recently identified as an inhibitory cytokine produced by natural Treg in mice, but not in humans...
  9. Marquet S, Doumbo O, Cabantous S, Poudiougou B, Argiro L, Safeukui I, et al. A functional promoter variant in IL12B predisposes to cerebral malaria. Hum Mol Genet. 2008;17:2190-5 pubmed publisher
    ..These results, together with the findings from immunological studies of low interferon-gamma and IL-12 levels in CM, support a protective role for the Th1 pathway in CM...

More Information

Publications84

  1. Ling P, Gately M, Gubler U, Stern A, Lin P, Hollfelder K, et al. Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity. J Immunol. 1995;154:116-27 pubmed
    IL-12, a heterodimeric cytokine, consists of two disulfide-linked subunits, p40 and p35. We investigated the role of p40 in ligand binding and signal transduction by expressing this subunit alone in COS cells...
  2. Wolf S, Temple P, Kobayashi M, Young D, Dicig M, Lowe L, et al. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol. 1991;146:3074-81 pubmed
    ..Purified NKSF was found to be a disulfide-linked heterodimeric protein composed of 35-kDa and 40-kDa subunits (p35 and p40). We now report the molecular cloning of cDNA for both subunits of NKSF from RPMI 8866 cellular RNA...
  3. Gubler U, Chua A, Schoenhaut D, Dwyer C, McComas W, Motyka R, et al. Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci U S A. 1991;88:4143-7 pubmed
    Cytotoxic lymphocyte maturation factor (CLMF) is a disulfide-bonded heterodimeric lymphokine that (i) acts as a growth factor for activated T cells independent of interleukin 2 and (ii) synergizes with suboptimal concentrations of ..
  4. Hayes M, Murphy F, Burd P. Interferon-gamma-dependent inducible expression of the human interleukin-12 p35 gene in monocytes initiates from a TATA-containing promoter distinct from the CpG-rich promoter active in Epstein-Barr virus-transformed lymphoblastoid cells. Blood. 1998;91:4645-51 pubmed
    ..IL-12) production by human monocytes is stringently regulated through the inducibility of both subunits, p35 and p40, and expression of p35 mRNA is the limiting factor for the secretion of the bioactive IL-12 p70 heterodimer...
  5. Sieburth D, Jabs E, Warrington J, Li X, Lasota J, LaForgia S, et al. Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5. Genomics. 1992;14:59-62 pubmed
    IL12 (formerly NKSF or CLMF) is a unique cytokine composed of two unrelated disulfide-linked subunits...
  6. De Jager P, Jia X, Wang J, de Bakker P, Ottoboni L, Aggarwal N, et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet. 2009;41:776-82 pubmed publisher
  7. Mirani M, Elenkov I, Volpi S, Hiroi N, Chrousos G, Kino T. HIV-1 protein Vpr suppresses IL-12 production from human monocytes by enhancing glucocorticoid action: potential implications of Vpr coactivator activity for the innate and cellular immunity deficits observed in HIV-1 infection. J Immunol. 2002;169:6361-8 pubmed
    ..potentiated glucocorticoid-induced suppression of both mRNA expression and secretion of IL-12 subunit p35 and IL-12 holo-protein, but not IL-12 subunit p40 or IL-10, by human monocytes/macrophages stimulated with LPS or ..
  8. Goriely S, Demonte D, Nizet S, De Wit D, Willems F, Goldman M, et al. Human IL-12(p35) gene activation involves selective remodeling of a single nucleosome within a region of the promoter containing critical Sp1-binding sites. Blood. 2003;101:4894-902 pubmed
    ..the regulation of human interleukin-12 (IL-12) synthesis, we determined the chromatin organization of the IL-12(p35) promoter region...
  9. Liu F, Tong F, He Y, Liu H. Detectable expression of IL-35 in CD4+ T cells from peripheral blood of chronic hepatitis B patients. Clin Immunol. 2011;139:1-5 pubmed publisher
    Epstein-Barr virus-induced gene 3 (Ebi3) and the p35 subunit of IL-12 have been reported to form a heterodimeric cytokine, named IL-35, in human and mouse...
  10. Kubin M, Kamoun M, Trinchieri G. Interleukin 12 synergizes with B7/CD28 interaction in inducing efficient proliferation and cytokine production of human T cells. J Exp Med. 1994;180:211-22 pubmed
  11. Chen T, Liang W, Gao L, Wang Y, Liu Y, Zhang L, et al. Association of single nucleotide polymorphisms in interleukin 12 (IL-12A and -B) with asthma in a Chinese population. Hum Immunol. 2011;72:603-6 pubmed publisher
    ..These results suggest that the SNPs in IL-12A rs568404 and IL-12B rs3212227 may individually and jointly contribute to the risk of asthma in a Chinese population. ..
  12. van de Wetering D, de Paus R, van Dissel J, van de Vosse E. IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T cell function differentially from IL-12. Int Immunol. 2009;21:145-53 pubmed publisher
  13. Liu X, Invernizzi P, Lu Y, Kosoy R, Lu Y, Bianchi I, et al. Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis. Nat Genet. 2010;42:658-60 pubmed publisher
    ..9 x 10(-11), odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 x 10(-10), OR = 1.63) and 17q12-21 (P = 1.7 x 10(-10), OR = 1.38). ..
  14. Li X, Mai J, Virtue A, Yin Y, Gong R, Sha X, et al. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines. PLoS ONE. 2012;7:e33628 pubmed publisher
    ..Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies. ..
  15. Fanales Belasio E, Moretti S, Nappi F, Barillari G, Micheletti F, Cafaro A, et al. Native HIV-1 Tat protein targets monocyte-derived dendritic cells and enhances their maturation, function, and antigen-specific T cell responses. J Immunol. 2002;168:197-206 pubmed
    ..Thus, Tat can act as both Ag and adjuvant, capable of driving T cell-mediated immune responses. ..
  16. Grzegorzewska A, Wobszal P, Sowińska A, Mostowska A, Jagodziński P. Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection. Mol Biol Rep. 2013;40:6899-911 pubmed publisher
  17. Park J, Cheong J, Kang J, Cho J, Yu S, Shin H, et al. [Association of interleukin-12 gene polymorphism with persistence of hepatitis B virus infection and hepatocellular carcinoma]. Korean J Gastroenterol. 2007;50:313-8 pubmed
    ..Further studies are needed to identify the host genetic factors in immune defense including cytokine gene polymorphisms of both IL-12A and IL-12B. ..
  18. Schoenhaut D, Chua A, Wolitzky A, Quinn P, Dwyer C, McComas W, et al. Cloning and expression of murine IL-12. J Immunol. 1992;148:3433-40 pubmed
    ..the murine subunits with their human counterparts revealed that the p40 subunits are more highly conserved than the p35 subunits (70% vs 60% identity, respectively). The sizes of the p35 and p40 subunit mRNA were estimated to be 1...
  19. Chen X, Han S, Wang S, Zhou X, Zhang M, Dong J, et al. Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women. Clin Cancer Res. 2009;15:400-5 pubmed publisher
    ..These findings suggest that IL12A rs568408 and IL12B rs3212227 may individually and jointly contribute to the risk of cervical cancer and may modify cervical cancer risk associated with parity, but these data need further validation. ..
  20. Smyth D, Plagnol V, Walker N, Cooper J, Downes K, Yang J, et al. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008;359:2767-77 pubmed publisher
    ..These data suggest that common biologic mechanisms, such as autoimmunity-related tissue damage and intolerance to dietary antigens, may be etiologic features of both diseases. ..
  21. Snijders A, Hilkens C, van der Pouw Kraan T, Engel M, Aarden L, Kapsenberg M. Regulation of bioactive IL-12 production in lipopolysaccharide-stimulated human monocytes is determined by the expression of the p35 subunit. J Immunol. 1996;156:1207-12 pubmed
    ..Bioactive IL-12 (p70) is composed of two subunits, p35, which is only secreted as part of the p70 dimer, and p40, which can also be secreted by itself...
  22. Majumder B, Janket M, Schafer E, Schaubert K, Huang X, Kan Mitchell J, et al. Human immunodeficiency virus type 1 Vpr impairs dendritic cell maturation and T-cell activation: implications for viral immune escape. J Virol. 2005;79:7990-8003 pubmed
    ..Taken together, these results indicate that HIV-1 Vpr may in part be responsible for HIV-1 immune evasion by inhibiting the maturation of costimulatory molecules and cytokines essential for immune activation. ..
  23. Kirino Y, Bertsias G, Ishigatsubo Y, Mizuki N, Tugal Tutkun I, Seyahi E, et al. Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1. Nat Genet. 2013;45:202-7 pubmed publisher
  24. Goriely S, Van Lint C, Dadkhah R, Libin M, De Wit D, Demonte D, et al. A defect in nucleosome remodeling prevents IL-12(p35) gene transcription in neonatal dendritic cells. J Exp Med. 2004;199:1011-6 pubmed
    ..into the inability of newborns to mount efficient Th1 responses, we analyzed the molecular basis of defective IL-12(p35) expression in human neonatal monocyte-derived dendritic cells (DCs)...
  25. Hoeve M, Savage N, De Boer T, Langenberg D, de Waal Malefyt R, Ottenhoff T, et al. Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. Eur J Immunol. 2006;36:661-70 pubmed
  26. Kim Y, Sung J, Ceglia I, Lee K, Ahn J, Halford J, et al. Phosphorylation of WAVE1 regulates actin polymerization and dendritic spine morphology. Nature. 2006;442:814-7 pubmed
    ..Our data suggest that phosphorylation/dephosphorylation of WAVE1 in neurons has an important role in the formation of the filamentous actin cytoskeleton, and thus in the regulation of dendritic spine morphology. ..
  27. Liu L, Xu Y, Liu Z, Chen J, Zhang Y, Zhu J, et al. IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population. Int J Cancer. 2011;128:1692-6 pubmed publisher
    ..Our findings indicate that IL12A rs568408 may contribute to the risk of HCC and modify HCC risk associated with HBV infection. ..
  28. Hirschfield G, Liu X, Xu C, Lu Y, Xie G, Lu Y, et al. Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N Engl J Med. 2009;360:2544-55 pubmed publisher
    ..Twin and family aggregation data suggest that there is a significant genetic predisposition to primary biliary cirrhosis, but the susceptibility loci are unknown...
  29. Ye L, Wang X, Metzger D, Riedel E, Montaner L, Ho W. Upregulation of SOCS-3 and PIAS-3 impairs IL-12-mediated interferon-gamma response in CD56 T cells in HCV-infected heroin users. PLoS ONE. 2010;5:e9602 pubmed publisher
    ..These findings provide compelling in vivo evidence that heroin use or heroin use plus HCV infection impairs CD56(+) T cell-mediated innate immune function, which may account for HCV infection and persistence in liver. ..
  30. Howell W, Turner S, Theaker J, Bateman A. Cytokine gene single nucleotide polymorphisms and susceptibility to and prognosis in cutaneous malignant melanoma. Eur J Immunogenet. 2003;30:409-14 pubmed
  31. Anand G, Vasanthakumar R, Mohan V, Babu S, Aravindhan V. Increased IL-12 and decreased IL-33 serum levels are associated with increased Th1 and suppressed Th2 cytokine profile in patients with diabetic nephropathy (CURES-134). Int J Clin Exp Pathol. 2014;7:8008-15 pubmed
    ..DN was associated with enhanced Th1 response and suppression of Th2 responses which might be due to inreased levels of IL-12 and decreased levels of IL-33 cytokines respectively. ..
  32. Nalbant A, Saygili T. IL12, IL10, IFN? and TNF? Expression in Human Primary Monocytes Stimulated with Bacterial Heat Shock GroEL (Hsp64) Protein. PLoS ONE. 2016;11:e0154085 pubmed publisher
    ..Therefore, A. actinomycetemcomitans's heat shock GroEL protein can modulate innate and adaptive immune responses and contribute to an inflammatory diseases pathology. ..
  33. Liu L, Huang Y, Huang Q, Zhao Z, Yu J, Wang L. Muscarinic acetylcholine M4 receptors play a critical role in oxotremorine-induced DARPP-32 phosphorylation at threonine 75 in isolated medium spiny neurons. Neuropharmacology. 2017;117:376-386 pubmed publisher
    ..The OX-induced time-dependent increase in DARPP-32 phosphorylation at Thr75 was accompanied by increased p35 and CDK5 activity...
  34. Romanos J, Barisani D, Trynka G, Zhernakova A, Bardella M, Wijmenga C. Six new coeliac disease loci replicated in an Italian population confirm association with coeliac disease. J Med Genet. 2009;46:60-3 pubmed publisher
    ..Our results may imply there is a genuine population difference across Europe regarding the loci contributing to CD. ..
  35. Austin S, Katusic Z. Loss of Endothelial Nitric Oxide Synthase Promotes p25 Generation and Tau Phosphorylation in a Murine Model of Alzheimer's Disease. Circ Res. 2016;119:1128-1134 pubmed
    ..Brain tissue from eNOS-/- mice had statistically higher ratios of p25/p35, indicative of increased cyclin-dependent kinase 5 activity as compared with wild-type (n=8, P<0.05)...
  36. Trajkov D, Arsov T, Petlichkovski A, Strezova A, Efinska Mladenovska O, Gogusev J, et al. Distribution of the 22 cytokine gene polymorphisms in healthy Macedonian population. Bratisl Lek Listy. 2009;110:7-17 pubmed
    ..020). The results of cytokine polymorphisms in Macedonian population can be used for anthropological comparisons, as well as for association studies with different diseases (Tab. 6, Ref. 34). Full Text (Free, PDF) www. bmj. sk. ..
  37. Erdei E, Kang H, Meisner A, White K, Pickett G, Baca C, et al. Polymorphisms in cytokine genes and serum cytokine levels among New Mexican women with and without breast cancer. Cytokine. 2010;51:18-24 pubmed publisher
    ..These findings might guide us to understand the presence of SNPs in cytokine genes and serum concentrations among breast cancer patients and potentially in other cancers. ..
  38. Kozela E, Juknat A, Gao F, Kaushansky N, Coppola G, Vogel Z. Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells. J Neuroinflammation. 2016;13:136 pubmed publisher
    ..These findings put forward mechanism by which CBD exerts its anti-inflammatory effects as well as explain the beneficial role of CBD in pathological memory T cells and in autoimmune diseases. ..
  39. Roszak A, Mostowska A, Sowińska A, Lianeri M, Jagodzinski P. Contribution of IL12A and IL12B polymorphisms to the risk of cervical cancer. Pathol Oncol Res. 2012;18:997-1002 pubmed
    ..Our studies confirmed that the IL12B 3'UTR A>C polymorphism may be a genetic risk factor for cervical cancer. ..
  40. Vasilescu A, Heath S, Ivanova R, Hendel H, Do H, Mazoyer A, et al. Genomic analysis of Th1-Th2 cytokine genes in an AIDS cohort: identification of IL4 and IL10 haplotypes associated with the disease progression. Genes Immun. 2003;4:441-9 pubmed
    ..The catalogue of SNP and haplotypes presented here will facilitate further genetic investigations of Th1-Th2 cytokines in AIDS and other immune-related disorders. ..
  41. Yang K. Postnatal Excitability Development and Innervation by Functional Transient Receptor Potential Vanilloid 1 (TRPV1) Terminals in Neurons of the Rat Spinal Sacral Dorsal Commissural Nucleus: an Electrophysiological Study. Mol Neurobiol. 2016;53:6033-6042 pubmed publisher
    ..SDCN neurons in neonatal (postnatal day (P) 1-2), young (P8-10), and adult rats (P35-40) have different electrophysiological properties...
  42. Luo F, Zhang J, Burke K, Miller R, Yang Y. The Activators of Cyclin-Dependent Kinase 5 p35 and p39 Are Essential for Oligodendrocyte Maturation, Process Formation, and Myelination. J Neurosci. 2016;36:3024-37 pubmed publisher
    ..including the noncanonical cyclin-dependent kinase 5 (Cdk5) whose functions are regulated by its activators p35 and p39...
  43. Shen T, Tsai C, Chang W, Wang S, Chao C, Hsiao C, et al. Association of Interleukin-12A rs568408 with Susceptibility to Asthma in Taiwan. Sci Rep. 2017;7:3199 pubmed publisher
    ..0085) among asthmatic patients. These results suggest that IL-12A rs568408 may contribute to the etiology and symptoms severity of asthma, indicating its usefulness as a predictive and diagnostic biomarker of asthma. ..
  44. Gorenec L, Zidovec Lepej S, Grgić I, Planinic A, Iscic Bes J, Vince A, et al. The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection. Microb Pathog. 2016;97:125-30 pubmed publisher
    ..Comparison of cytokine expression between two stages of infection showed a significant decrease in IL-9 concentration. This study showed changes in cytokine profiles on both gene and protein levels in different stages of HIV-infection. ..
  45. Alaki E, Aljobair F, Alaklobi F, Al Shamrani M, Al Zahim F, Dongues A, et al. Chronic Disseminated Salmonellosis in a Patient With Interleukin-12p40 Deficiency. Pediatr Infect Dis J. 2018;37:90-93 pubmed publisher
    Interleukin (IL)-12 is composed of p35 and p40 subunits; in this case, IL-12p40 deficiency is a rare genetic etiology of Mendelian susceptibility to mycobacterial disease...
  46. Haraguchi S, Day N, Nelson R, Emmanuel P, Duplantier J, Christodoulou C, et al. Interleukin 12 deficiency associated with recurrent infections. Proc Natl Acad Sci U S A. 1998;95:13125-9 pubmed
  47. De Jager P, Chibnik L, Cui J, Reischl J, Lehr S, Simon K, et al. Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score. Lancet Neurol. 2009;8:1111-9 pubmed publisher
    ..Future iterations of the wGRS might therefore make a contribution to algorithms that can predict a diagnosis of MS in a clinical or research setting. ..
  48. Ji Y, Zhuang P, Ji Z, Wu Y, Gu Y, Gao X, et al. TFP5 peptide, derived from CDK5-activating cofactor p35, provides neuroprotection in early-stage of adult ischemic stroke. Sci Rep. 2017;7:40013 pubmed publisher
    ..CDK5 activity increases when its cofactor p35 cleaves into p25 during ischemia...
  49. Chen J, Huang A, Chen S, Wu J, Wu W, Chiang H, et al. Interleukin-27 and interleukin-12 augment activation of distinct cord blood natural killer cells responses via STAT3 pathways. J Formos Med Assoc. 2012;111:275-83 pubmed publisher
    ..From previous results, we summarize our current understanding of the augmentation of distinct regulation of NK cells by IL-27 and IL-12. ..
  50. Bal S, Bernink J, Nagasawa M, Groot J, Shikhagaie M, Golebski K, et al. IL-1?, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs. Nat Immunol. 2016;17:636-45 pubmed publisher
    ..We propose that IL-12 and IL-4 govern ILC2 functional identity and that their imbalance results in the perpetuation of type 1 or type 2 inflammation. ..
  51. Yuan Y, Fan D, Zhu S, Yang J, Chen J. Identification and characterization of host cell proteins interacting with Scylla serrata reovirus non-structural protein p35. Virus Genes. 2017;53:317-322 pubmed publisher
    We have previously shown that non-structural protein p35, encoded by Scylla serrata reovirus (SsRV) S10, may act as a viroporin...
  52. Liu J, Guan X, Tamura T, Ozato K, Ma X. Synergistic activation of interleukin-12 p35 gene transcription by interferon regulatory factor-1 and interferon consensus sequence-binding protein. J Biol Chem. 2004;279:55609-17 pubmed
    ..The defect is also observed at the level of IL-12 p40 and p35 mRNA expression. Transcriptional analyses revealed that ICSBP is a potent activator of the IL-12 p35 gene...
  53. Forte G, Ragonese P, Salemi G, Scola L, Candore G, D Amelio M, et al. Search for genetic factors associated with susceptibility to multiple sclerosis. Ann N Y Acad Sci. 2006;1067:264-9 pubmed
    ..It is reasonable to suppose that the cytokine single-nucleotide polymorphisms (SNPs) studied must be considered against a larger genetic background involving other functional SNPs of Th1 regulator elements such as IL-21 and IL-23. ..
  54. Yilmaz V, Tütüncü Y, Bariş Hasbal N, Parman Y, Serdaroglu P, Deymeer F, et al. Polymorphisms of interferon-gamma, interleukin-10, and interleukin-12 genes in myasthenia gravis. Hum Immunol. 2007;68:544-9 pubmed
    ..These data suggest that some cytokine gene polymorphisms may contribute to susceptibility to or antibody production in MG. These findings need to be replicated in further studies. ..
  55. Shi M, Wei J, Dong J, Meng W, Ma J, Wang T, et al. Function of interleukin-17 and -35 in the blood of patients with hepatitis B-related liver cirrhosis. Mol Med Rep. 2015;11:121-6 pubmed publisher
    ..Serum IL-35 levels were negatively correlated with albumin, but not with Child-Pugh grade, ALT and TBIL. IL-17 and IL-35 may be critically involved in the pathogenesis of hepatitis B-related LC. ..
  56. Zhao R, Elder R, Bukrinsky M. Interactions of HIV-1 viral protein R with host cell proteins. Adv Pharmacol. 2007;55:233-60 pubmed
  57. Tagawa T, Albanese M, Bouvet M, Moosmann A, Mautner J, Heissmeyer V, et al. Epstein-Barr viral miRNAs inhibit antiviral CD4+ T cell responses targeting IL-12 and peptide processing. J Exp Med. 2016;213:2065-80 pubmed publisher
  58. Albu D, Jones Trower A, Woron A, Stellrecht K, Broder C, Metzger D. Intranasal vaccination using interleukin-12 and cholera toxin subunit B as adjuvants to enhance mucosal and systemic immunity to human immunodeficiency virus type 1 glycoproteins. J Virol. 2003;77:5589-97 pubmed
  59. Louw du Toit R, Hapgood J, Africander D. Medroxyprogesterone acetate differentially regulates interleukin (IL)-12 and IL-10 in a human ectocervical epithelial cell line in a glucocorticoid receptor (GR)-dependent manner. J Biol Chem. 2014;289:31136-49 pubmed publisher
    ..These results suggest that both P4 and MPA may modulate inflammation in the ectocervix via this genomic mechanism. ..
  60. Plan s R, Bahraoui E. HIV-1 Tat protein induces the production of IDO in human monocyte derived-dendritic cells through a direct mechanism: effect on T cells proliferation. PLoS ONE. 2013;8:e74551 pubmed publisher
    ..By inducing IDO, Tat protein may be considered, as a viral pathogenic factor, in the dysregulation of the DC functions during HIV-1 infection...
  61. Navaglia F, Basso D, Zambon C, Ponzano E, Caenazzo L, Gallo N, et al. Interleukin 12 gene polymorphisms enhance gastric cancer risk in H pylori infected individuals. J Med Genet. 2005;42:503-10 pubmed
  62. Prencipe G, Caiello I, Pascarella A, Grom A, Bracaglia C, Chatel L, et al. Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome. J Allergy Clin Immunol. 2018;141:1439-1449 pubmed publisher
    ..The decrease in CXCL9 and CXCL10 levels paralleled the decrease in serum levels of proinflammatory cytokines and ferritin. These results provide evidence for a pathogenic role of IFN-γ in the setting of MAS. ..
  63. Beretta L, Santaniello A, Mayo M, Cappiello F, Marchini M, Scorza R. A 3-factor epistatic model predicts digital ulcers in Italian scleroderma patients. Eur J Intern Med. 2010;21:347-53 pubmed publisher
    ..Owing to the limited number of patients included in the study, future research are needed to replicate our statistical findings as well as to better determine their functional meaning. ..
  64. Cui B, Liu W, Wang X, Chen Y, Du Q, Zhao X, et al. Brucella Omp25 Upregulates miR-155, miR-21-5p, and miR-23b to Inhibit Interleukin-12 Production via Modulation of Programmed Death-1 Signaling in Human Monocyte/Macrophages. Front Immunol. 2017;8:708 pubmed publisher
    ..of Omp25 protein inhibited TLR agonists-induced IL-12 p70 production through suppression of both IL-12 p40 and p35 subunit expression in THP-1 cells...
  65. Fogel O, Rivière E, Seror R, Nocturne G, Boudaoud S, Ly B, et al. Role of the IL-12/IL-35 balance in patients with Sjögren syndrome. J Allergy Clin Immunol. 2018;142:258-268.e5 pubmed publisher
    ..Serum IL-35 levels were associated with low disease activity, in contrast with serum IL-12p70 levels, which were associated with more active disease. ..
  66. Rezai O, Khodadadi A, Heike Y, Mostafai A, Gerdabi N, Rashno M, et al. Assessment of Relationship between Wilms' Tumor Gene (WT1) Expression in Peripheral Blood of Acute Leukemia Patients and Serum IL-12 and C3 Levels. Asian Pac J Cancer Prev. 2015;16:7303-7 pubmed
    ..Wt1 expression levels in patients are inversely related with serum levels of IL-12 and C3. ..
  67. Johansson U, Cooke S, Londei M. Identification of a new isoform of human IL-12 p35 mRNA. Eur J Immunogenet. 2002;29:439-44 pubmed
    This study has identified an alternate mRNA isoform of the human interleukin-12 p35 gene differing from normal p35 transcripts by the deletion of exon 3...
  68. Zhang R, Fichtenbaum C, Hildeman D, Lifson J, Chougnet C. CD40 ligand dysregulation in HIV infection: HIV glycoprotein 120 inhibits signaling cascades upstream of CD40 ligand transcription. J Immunol. 2004;172:2678-86 pubmed
    ..Clear elucidation of mechanism(s) may well lead to the development of novel immunotherapeutic approaches to HIV infection. ..
  69. Amirzargar A, Naroueynejad M, Khosravi F, Dianat S, Dianat S, Rezaei N, et al. Cytokine single nucleotide polymorphisms in Iranian populations. Eur Cytokine Netw. 2008;19:104-12 pubmed publisher
    ..Although some significant differences were observed for some cytokines, it seems that the cytokine gene polymorphism profile of the Iranian population is similar to that of Caucasians, particularly the Italian population. ..
  70. Yamamoto K, Shibata F, Miyasaka N, Miura O. The human perforin gene is a direct target of STAT4 activated by IL-12 in NK cells. Biochem Biophys Res Commun. 2002;297:1245-52 pubmed
    ..These results indicate that the IL-12-induced expression of the perforin gene in NK cells is directly regulated by STAT4, which binds, most likely as a homo-tetramer, to the tandem STAT-binding sequences in the perforin gene promoter. ..
  71. Ross O, Curran M, Meenagh A, Williams F, Barnett Y, Middleton D, et al. Study of age-association with cytokine gene polymorphisms in an aged Irish population. Mech Ageing Dev. 2003;124:199-206 pubmed
    ..These findings would suggest that polymorphism of cytokine genes may not play as crucial a role in healthy ageing as previously believed. ..
  72. Nakano S, Morimoto S, Suzuki S, Tsushima H, Yamanaka K, Sekigawa I, et al. Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis. Rheumatology (Oxford). 2015;54:1498-506 pubmed publisher
    ..It consists of EBV-induced gene 3 (EBI3) and IL-12α chain p35. We investigated whether IL-35 enhances the in vitro immunosuppressive function of peripheral blood isolated from ..
  73. Sima X, Xu J, Li Q, Luo L, Liu J, You C. Gene-gene interactions between interleukin-12A and interleukin-12B with the risk of brain tumor. DNA Cell Biol. 2012;31:219-23 pubmed publisher
    ..05-6.50). This study provides evidence that IL-12A rs2243115 may be associated with the risk of brain tumor. Additionally, gene-gene interactions of IL-12A rs2243115 and IL-12B rs3212227 may contribute to brain tumor susceptibility. ..
  74. Bihaqi S, Eid A, Zawia N. Lead exposure and tau hyperphosphorylation: An in vitro study. Neurotoxicology. 2017;62:218-223 pubmed publisher
    ..the protein expression of total tau, site-specific tau hyperphosphorylation, cyclin dependent kinase 5 (CDK5) and p35/p25 at selected time points (24-144h), after Pb exposure had ceased...
  75. Cheng J, Imanishi H, Morisaki H, Liu W, Nakamura H, Morisaki T, et al. Recombinant HBsAg inhibits LPS-induced COX-2 expression and IL-18 production by interfering with the NFkappaB pathway in a human monocytic cell line, THP-1. J Hepatol. 2005;43:465-71 pubmed
    ..These results showed a novel anti-inflammatory property of rHBsAg which involves inhibition of COX-2 and suggested that hepatitis B virus may regulate IFN-gamma production by inhibiting IL-18 and IL-12 production. ..