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Gene Review

IFNG  -  interferon, gamma

Macaca mulatta

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Disease relevance of IFNG


High impact information on IFNG

  • Protection was associated with marked increases in plasma levels of interferon-gamma (IFN-gamma), and relative increases of lymphoid cell messenger RNA coding for IFN-gamma and several other cytokines [6].
  • We speculate that rIL-12 protects monkeys through IFN-gamma-dependent elimination of P. cynomolgi-infected hepatocytes [6].
  • SIV-specific stimulation of lymphocytes from vaccinated macaques resulted in secretion of interferon-gamma, IL-2, regulated-upon-activation, normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta but not IL-4 or IL-10 [7].
  • Macrophage/monocytes in vitro synthesized [13C6]quinolinic acid from [13C6]L-tryptophan, particularly when stimulated by interferon-gamma [8].
  • The LEA29Y-based regimen prevented the priming of anti-donor T- and B-cell responses, as detected by interferon-gamma enzyme-linked immunospot and allo-antibody production, respectively [9].

Chemical compound and disease context of IFNG


Biological context of IFNG


Anatomical context of IFNG

  • We propose that SIV replication in vivo initiates IFN-gamma-driven positive-feedback loops in lymphoid tissues that disrupt the trafficking of effector T lymphocytes and lead to chronic local inflammation, thereby contributing to immunopathogenesis [2].
  • CONCLUSIONS: In this model, peritransplant induction of tolerance is promoted by efficient elimination of sessile lymph node T cells and control of the proinflammatory IFN-gamma response by a mechanism that appears to involve resistance to IL-12 [17].
  • Oral immunization of macaques with p55gag plus CT induced interferon-gamma-secreting Th1-type and select Th2-type cytokine-producing CD4+ T helper cells, which most likely accounted for the induction of p55-specific systemic IgG and mucosal IgA responses [18].
  • We also found a constitutively low expression of major histocompatibility complex (MHC) class II by cultured astrocytes which was significantly enhanced by lipopolysaccharide (LPS), interferon gamma (IFN-gamma), or tumor necrosis factor alpha (TNF-alpha) treatments [19].
  • Leukocyte TNF-alpha secretion in response to viral antigen and PBMC production of interferon gamma (IFNgamma), IL-6, and IL-10 following exposure to mitogen or antigen were unaffected by previous TCDD treatment [20].

Associations of IFNG with chemical compounds

  • DSG was shown to inhibit IL-12-driven IFN-gamma production by a mechanism associated with inhibition of nuclear factor kappa-B [17].
  • Kynurenine aminotransferase activity was measurable in all cell types examined but was unaffected by interferon-gamma [4].
  • This hypothesis is further supported by the findings that interferon-gamma significantly inhibits luteal basal and hCG-stimulated progesterone production and also stimulates basal and hCG-induced tPA activity [21].
  • Proliferative responses were observed with both isopentenylpyrophosphate and alendronate, but stronger interferon-gamma secretory responses were observed with isopentenylpyrophosphate [22].
  • Cryopreserved cells were as functional as fresh cells in heparinized blood samples and compared to EDTA, heparin was the better anticoagulant for yielding IFN-gamma+ cells [16].

Regulatory relationships of IFNG


Other interactions of IFNG

  • Elevated levels of IL-6 cDNA and, to a lesser extent, interferon gamma were detected in three of three nonhuman primates with persistent infection with B burgdorferi, whereas the brains of three uninfected animals and undetectable levels of gene expression of these cytokines [24].
  • Reactivity with the following antigens was assessed: MHC class I, II-DR, -DQ, and -DP antigens; leukocyte markers CD1, CD2, CD3, CD4, CD8, CD14, CD16, CD25, CD57; a proliferation associated nuclear antigen; interferon-gamma and tumor necrosis factor-alpha [25].
  • Our results suggest that TGF-beta 1 and its receptors may play an important regulatory role in maintaining CL function, and that IFN-gamma or TNF-alpha is capable of inhibiting their expression in the CL [23].

Analytical, diagnostic and therapeutic context of IFNG

  • Samples of brain tissue were screened for IL-6 and interferon gamma using RT-PCR-ELISA, a technique that uses RT-PCR, subsequent hybridization of the PCR product with a biotinylated probe, and capture and ELISA readout of hybridization product [24].
  • Synergistic immunosuppressive effects of monoclonal antibodies specific for interferon-gamma and tumor necrosis factor alpha. A skin transplantation study in the rhesus monkey [13].
  • The secreted proteins were revealed to have antiviral activity up to 10(8) units/ml characteristic of authentic IFNgamma by a bioassay of a cytopathic effect reduction assay [26].
  • Molecular cloning and expression of cynomolgus monkey interferon-gamma cDNA [26].
  • HIV-specific interferon-gamma-producing CD4+ and CD8+ T-cell responses were measured before and after the fourth and fifth immunizations by both intracellular cytokine (ICC) and ELISPOT techniques; responses were detected in three of the four immunized animals [27].


  1. Replication, immunogenicity, and protective properties of live-attenuated simian immunodeficiency viruses expressing interleukin-4 or interferon-gamma. Stahl-Hennig, C., Gundlach, B.R., Dittmer, U., ten Haaft, P., Heeney, J., Zou, W., Emilie, D., Sopper, S., Uberla, K. Virology (2003) [Pubmed]
  2. Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome. Reinhart, T.A., Fallert, B.A., Pfeifer, M.E., Sanghavi, S., Capuano, S., Rajakumar, P., Murphey-Corb, M., Day, R., Fuller, C.L., Schaefer, T.M. Blood (2002) [Pubmed]
  3. Immunomodulation and adenoviral gene transfer to the lungs of nonhuman primates. Shean, M.K., Baskin, G., Sullivan, D., Schurr, J., Cavender, D.E., Shellito, J.E., Schwarzenberger, P.O., Kolls, J.K. Hum. Gene Ther. (2000) [Pubmed]
  4. Metabolism of L-tryptophan to kynurenate and quinolinate in the central nervous system: effects of 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilate. Naritsin, D.B., Saito, K., Markey, S.P., Chen, C.Y., Heyes, M.P. J. Neurochem. (1995) [Pubmed]
  5. Granulocyte contamination dramatically inhibits spot formation in AIDS virus-specific ELISpot assays: analysis and strategies to ameliorate. De Rose, R., Taylor, E.L., Law, M.G., van der Meide, P.H., Kent, S.J. J. Immunol. Methods (2005) [Pubmed]
  6. Sterile protection of monkeys against malaria after administration of interleukin-12. Hoffman, S.L., Crutcher, J.M., Puri, S.K., Ansari, A.A., Villinger, F., Franke, E.D., Singh, P.P., Finkelman, F., Gately, M.K., Dutta, G.P., Sedegah, M. Nat. Med. (1997) [Pubmed]
  7. Immunization with live attenuated simian immunodeficiency virus induces strong type 1 T helper responses and beta-chemokine production. Gauduin, M.C., Glickman, R.L., Ahmad, S., Yilma, T., Johnson, R.P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  8. Poliovirus induces indoleamine-2,3-dioxygenase and quinolinic acid synthesis in macaque brain. Heyes, M.P., Saito, K., Jacobowitz, D., Markey, S.P., Takikawa, O., Vickers, J.H. FASEB J. (1992) [Pubmed]
  9. Calcineurin inhibitor-free CD28 blockade-based protocol protects allogeneic islets in nonhuman primates. Adams, A.B., Shirasugi, N., Durham, M.M., Strobert, E., Anderson, D., Rees, P., Cowan, S., Xu, H., Blinder, Y., Cheung, M., Hollenbaugh, D., Kenyon, N.S., Pearson, T.C., Larsen, C.P. Diabetes (2002) [Pubmed]
  10. Measles virus infection of rhesus macaques affects neutrophil expression of IL-12 and IL-10. Hoffman, S.J., Polack, F.P., Hauer, D.A., Griffin, D.E. Viral Immunol. (2003) [Pubmed]
  11. Fever induced by Escherichia coli or intrahypothalamic prostaglandin E2 enhances interferon-gamma synthesis. Taylor, M.W., Wei, K.A., Downing, J.F., Elizondo, R., Lundgren, E. J. Interferon Res. (1990) [Pubmed]
  12. Cytokine responses during acute simian Plasmodium cynomolgi and Plasmodium knowlesi infections. Praba-Egge, A.D., Montenegro, S., Cogswell, F.B., Hopper, T., James, M.A. Am. J. Trop. Med. Hyg. (2002) [Pubmed]
  13. Synergistic immunosuppressive effects of monoclonal antibodies specific for interferon-gamma and tumor necrosis factor alpha. A skin transplantation study in the rhesus monkey. Stevens, H.P., van der Kwast, T.H., van der Meide, P.H., Vuzevski, V.D., Buurman, W.A., Jonker, M. Transplantation (1990) [Pubmed]
  14. Activation of T lymphocytes for adhesion and cytokine expression by toxin-conjugated anti-CD3 monoclonal antibodies. Hamawy, M.M., Tsuchida, M., Manthei, E.R., Dong, Y., Fechner, J.E., Knechtle, J.S. Transplantation (1999) [Pubmed]
  15. Evaluation of combination DNA/replication-competent Ad-SIV recombinant immunization regimens in rhesus macaques. Malkevitch, N., Rohne, D., Pinczewski, J., Aldrich, K., Kalyanaraman, V.S., Letvin, N.L., Robert-Guroff, M. AIDS Res. Hum. Retroviruses (2004) [Pubmed]
  16. Detection of antigen-specific T cell interferon gamma expression by ELISPOT and cytokine flow cytometry assays in rhesus macaques. Pahar, B., Li, J., Rourke, T., Miller, C.J., McChesney, M.B. J. Immunol. Methods (2003) [Pubmed]
  17. Peritransplant tolerance induction with anti-CD3-immunotoxin: a matter of proinflammatory cytokine control. Contreras, J.L., Wang, P.X., Eckhoff, D.E., Lobashevsky, A.L., Asiedu, C., Frenette, L., Robbin, M.L., Hubbard, W.J., Cartner, S., Nadler, S., Cook, W.J., Sharff, J., Shiloach, J., Thomas, F.T., Neville, D.M., Thomas, J.M. Transplantation (1998) [Pubmed]
  18. Mucosal Th1- versus Th2-type responses for antibody- or cell-mediated immunity to simian immunodeficiency virus in rhesus macaques. McGhee, J.R., Kiyono, H., Kubota, M., Kawabata, S., Miller, C.J., Lehner, T., Imaoka, K., Fujihashi, K. J. Infect. Dis. (1999) [Pubmed]
  19. Obtention and characterization of primary astrocyte and microglial cultures from adult monkey brains. Guillemin, G., Boussin, F.D., Croitoru, J., Franck-Duchenne, M., Le Grand, R., Lazarini, F., Dormont, D. J. Neurosci. Res. (1997) [Pubmed]
  20. Increased tumor necrosis factor-alpha production by peripheral blood leukocytes from TCDD-exposed rhesus monkeys. Rier, S.E., Coe, C.L., Lemieux, A.M., Martin, D.C., Morris, R., Lucier, G.W., Clark, G.C. Toxicol. Sci. (2001) [Pubmed]
  21. Studies on the role of plasminogen activators and plasminogen activator inhibitor type-1 in rat corpus luteum of pregnancy. Liu, Y.X., Chen, Y.X., Shi, F.W., Feng, Q. Biol. Reprod. (1995) [Pubmed]
  22. The Vgamma2/Vdelta2 T-cell repertoire in Macaca fascicularis: functional responses to phosphoantigen stimulation by the Vgamma2/Jgamma1.2 subset. Cairo, C., Propp, N., Hebbeler, A.M., Colizzi, V., Pauza, C.D. Immunology (2005) [Pubmed]
  23. IFN-gamma and TNF-alpha inhibit expression of TGF-beta-1, its receptors TBETAR-I and TBETAR-II in the corpus luteum of PMSG/hCG treated rhesus monkey. Gao, H., Chen, X.L., Zhang, Z.H., Song, X.X., Hu, Z.Y., Liu, Y.X. Front. Biosci. (2005) [Pubmed]
  24. Interleukin-6 is expressed at high levels in the CNS in Lyme neuroborreliosis. Pachner, A.R., Amemiya, K., Delaney, E., O'Neill, T., Hughes, C.A., Zhang, W.F. Neurology (1997) [Pubmed]
  25. Monoclonal antibodies for immunohistochemical labeling of immunocompetent cells in frozen sections of rhesus monkey tissues. Stevens, H.P., van der Kwast, T.H., Timmermans, A., Stouten, N., Jonker, M. J. Med. Primatol. (1991) [Pubmed]
  26. Molecular cloning and expression of cynomolgus monkey interferon-gamma cDNA. Tatsumi, M., Sata, T. Int. Arch. Allergy Immunol. (1997) [Pubmed]
  27. Vaccination with gp120-depleted HIV-1 plus immunostimulatory CpG oligodeoxynucleotides in incomplete Freund's adjuvant stimulates cellular and humoral immunity in rhesus macaques. Silvera, P., Savary, J.R., Livingston, V., White, J., Manson, K.H., Wyand, M.H., Salk, P.L., Moss, R.B., Lewis, M.G. Vaccine (2004) [Pubmed]
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