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Gene Review

IFNG  -  interferon, gamma

Gallus gallus

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Disease relevance of IFNG

  • A rabbit antiserum to E. coli derived ChIFN-gamma effectively neutralized the macrophage-activating factor activity secreted by concanavalin A-induced spleen cells and various T cell lines, suggesting that IFN-gamma is the major macrophage-activating factor of the chicken [1].
  • An interferon-gamma-binding protein of novel structure encoded by the fowlpox virus [2].
  • In a 45-day BALB/c mouse model of visceral leishmaniasis, complete elimination of spleen parasite burden was achieved by cystatin in synergistic activation with a suboptimal dose of IFN-gamma [3].
  • Here we show that the currently circulating H9N2 influenza viruses provide chickens with cross-reactive protective immunity against the currently circulating H5N1 influenza viruses and that this protective immunity is closely related to the percentage of pulmonary CD8(+) T cells expressing gamma interferon (IFN-gamma) [4].
  • The role of intestinal lymphocytes and gamma interferon (IFN-gamma) production in protective immunity to Eimeria tenella infection was evaluated in two inbred strains of chickens (SC and TK) that display different patterns of susceptibility to coccidiosis [5].

High impact information on IFNG

  • Altogether, these data indicate that the drop of IL-2 production and T-cell proliferation, as well as the up regulation of IL-4 and IFN-gamma production, are complex manifestations of an evolving T-cell response [6].
  • IFN-gamma was almost completely produced by CD4+ T cells [7].
  • These results suggest that IRF-10 plays a role in the late stages of an immune defense by regulating the expression some of the IFN-gamma target genes in the absence of a cytotoxic effect [8].
  • Sterile immunity can be provided against the pre-erythrocytic stages of malaria by IFN-gamma-secreting CD8(+) T cells that recognize parasite-infected hepatocytes [9].
  • In this study, we characterize a Th1-like regulatory system focusing on the IL-18-regulated IFN-gamma secretion [10].

Chemical compound and disease context of IFNG


Biological context of IFNG


Anatomical context of IFNG

  • IL-8 mRNA responses were observed after infection with low and with high infection doses, but no IFN-gamma and TGF-beta mRNA responses were found in the duodenum [19].
  • In contrast to the case with promastigotes, cystatin and IFN-gamma inhibited the growth of amastigotes in macrophages [3].
  • Modulation of human polymorphonuclear leukocyte IgG Fc receptors and Fc receptor-mediated functions by IFN-gamma and glucocorticoids [16].
  • Cystatins up-regulate nitric oxide release from interferon-gamma-activated mouse peritoneal macrophages [20].
  • Both FcR expression and heteroantibody-mediated cytotoxicity were increased by culturing monocytes or U937 with IFN-gamma [21].

Associations of IFNG with chemical compounds

  • A 6-fold increase in NO production was observed with 0.5 microM chicken cystatin, a natural cysteine protease inhibitor, in IFN-gamma-activated macrophages [3].
  • In addition, we have demonstrated the ability of both IL-4 and IFN-gamma to enhance the ability of macrophages to bind substance P as measured by radiolabeled binding assay [22].
  • NO and 1,25-(OH)2D3 production by HD-11 cells was stimulated severalfold by the macrophage stimulators interferon-gamma and lipopolysaccharide and by an autologous, nonlipid, heat-labile factor with an apparent molecular mass approximately 10,000 daltons [23].
  • Consistent with mammalian IFN-gamma, the nitrite-inducing activity was found to be heat labile, with over 90% of the activity lost within 5 minutes of heating [24].
  • At 35 degrees C, spontaneous refolding of acid-denatured IFN-gamma was found to be dependent on the presence of guanidinium hydrochloride (0.15-0.25 M) or NaCl (0.1-0.2 M) [25].

Regulatory relationships of IFNG

  • IFN-gamma priming of chicken heterophils upregulates the expression of proinflammatory and Th1 cytokine mRNA following receptor-mediated phagocytosis of Salmonella enterica serovar enteritidis [26].
  • In this study, procaterol dose-dependently inhibited IFN-gamma production of peripheral blood mononuclear cells stimulated with ovalbumin in patients with hen's egg-sensitive atopic dermatitis, without inhibition of proliferative responses of peripheral blood mononuclear cells [15].

Other interactions of IFNG

  • After cultivation of 7h, the expression of IL-2 mRNA in the cell, 24h, IFN-gamma mRNA, were determined by semi-quantitative RT-PCR assay [27].
  • The sequence of the chicken interferon-gamma (ifn-gamma) gene was determined, one of the first non-mammalian cytokine gene structures to be elucidated [28].
  • We characterized T-cell subsets in the duodenum by means of FACS-analyses, lymphocyte proliferation assays with spleen lymphocytes and the mRNA profiles of different cytokines (TGF-beta2, -4, IFN-gamma, IL-2, -6, -8 and -18) in the duodenum by means of real-time PCR [19].
  • In contrast, CD4(+) cells only expressed highest levels of IL-10 after E. acervulina infection, whereas these cells produced abundant transcripts for IFN-gamma, IL-3, IL-15, and MIF after E. tenella infection [29].
  • When lymphocyte subpopulations were similarly analyzed, IFN-gamma, IL-2, IL-3, IL-15, and MIF were most highly increased in TCR2(+) cells following E. acervulina infection, while TCR1(+) cells only expressed high levels of IL-16 following E. tenella infection [29].

Analytical, diagnostic and therapeutic context of IFNG

  • Using various biological assays, we detected a chicken interferon-gamma (chIFN-gamma)-neutralizing activity in supernatants of fowlpox virus (FPV)-infected cells that could be destroyed by trypsin treatment [2].
  • The conferred antiviral state required at least 7 h to develop in target cells and was totally inhibited by the presence of antibody to mouse interferon alpha/beta but not to interferon gamma in the cocultures [30].
  • Using this organ culture assay, which more closely mimics the situation in vivo, we confirmed the tumor-selective cytotoxic effects of combined treatment with TNF and IFN-gamma as observed in separate cultures of malignant and non-malignant cells on "artificial" substrate [11].
  • Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-gamma [31].
  • The former is based on the conversion by excess alpha-casein of any population of unfolded IFN-gamma into one that escapes antibody recognition by subsequent ELISA [25].


  1. Biological properties of recombinant chicken interferon-gamma. Weining, K.C., Schultz, U., Münster, U., Kaspers, B., Staeheli, P. Eur. J. Immunol. (1996) [Pubmed]
  2. An interferon-gamma-binding protein of novel structure encoded by the fowlpox virus. Puehler, F., Schwarz, H., Waidner, B., Kalinowski, J., Kaspers, B., Bereswill, S., Staeheli, P. J. Biol. Chem. (2003) [Pubmed]
  3. Successful therapy of lethal murine visceral leishmaniasis with cystatin involves up-regulation of nitric oxide and a favorable T cell response. Das, L., Datta, N., Bandyopadhyay, S., Das, P.K. J. Immunol. (2001) [Pubmed]
  4. Protective cross-reactive cellular immunity to lethal A/Goose/Guangdong/1/96-like H5N1 influenza virus is correlated with the proportion of pulmonary CD8(+) T cells expressing gamma interferon. Seo, S.H., Peiris, M., Webster, R.G. J. Virol. (2002) [Pubmed]
  5. Eimeria tenella infection induces local gamma interferon production and intestinal lymphocyte subpopulation changes. Yun, C.H., Lillehoj, H.S., Choi, K.D. Infect. Immun. (2000) [Pubmed]
  6. Specific T-cell tolerance may reflect selective activation of lymphokine synthesis. Vidard, L., Colarusso, L.J., Benacerraf, B. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  7. Administration of interleukin 12 in combination with type II collagen induces severe arthritis in DBA/1 mice. Germann, T., Szeliga, J., Hess, H., Störkel, S., Podlaski, F.J., Gately, M.K., Schmitt, E., Rüde, E. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  8. A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein. Nehyba, J., Hrdlicková, R., Burnside, J., Bose, H.R. Mol. Cell. Biol. (2002) [Pubmed]
  9. Enhanced CD8+ T cell immune responses and protection elicited against Plasmodium berghei malaria by prime boost immunization regimens using a novel attenuated fowlpox virus. Anderson, R.J., Hannan, C.M., Gilbert, S.C., Laidlaw, S.M., Sheu, E.G., Korten, S., Sinden, R., Butcher, G.A., Skinner, M.A., Hill, A.V. J. Immunol. (2004) [Pubmed]
  10. IL-18 stimulates the proliferation and IFN-gamma release of CD4+ T cells in the chicken: conservation of a Th1-like system in a nonmammalian species. Göbel, T.W., Schneider, K., Schaerer, B., Mejri, I., Puehler, F., Weigend, S., Staeheli, P., Kaspers, B. J. Immunol. (2003) [Pubmed]
  11. Tumor-selective cytotoxic effects of murine tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) in organ culture of B16 melanoma cells and heart tissue. Mareel, M., Dragonetti, C., Tavernier, J., Fiers, W. Int. J. Cancer (1988) [Pubmed]
  12. Nitric oxide inhibits Marek's disease virus replication but is not the single decisive factor in interferon-gamma-mediated viral inhibition. Djeraba, A., Bernardet, N., Dambrine, G., Quéré, P. Virology (2000) [Pubmed]
  13. Analysis of disease resistance-associated parameters in broiler chickens challenged with Eimeria maxima. Zhu, J.J., Lillehoj, H.S., Allen, P.C., Yun, C.H., Pollock, D., Sadjadi, M., Emara, M.G. Poult. Sci. (2000) [Pubmed]
  14. Expression and functional characterization of recombinant chicken interferon-gamma. Song, K.D., Lillehoj, H.S., Choi, K.D., Zarlenga, D., Han, J.Y. Vet. Immunol. Immunopathol. (1997) [Pubmed]
  15. Inhibition of interferon-gamma production from lymphocytes stimulated with food antigens by a beta 2-agonist, procaterol, in patients with food-sensitive atopic dermatitis. Kondo, N., Shinbara, M., Inoue, R., Fukao, T., Kaneko, H., Teramoto, T., Tashita, H. Journal of investigational allergology & clinical immunology : official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología. (1997) [Pubmed]
  16. Modulation of human polymorphonuclear leukocyte IgG Fc receptors and Fc receptor-mediated functions by IFN-gamma and glucocorticoids. Petroni, K.C., Shen, L., Guyre, P.M. J. Immunol. (1988) [Pubmed]
  17. Cadmium blocks receptor-mediated Jak/STAT signaling in neurons by oxidative stress. Monroe, R.K., Halvorsen, S.W. Free Radic. Biol. Med. (2006) [Pubmed]
  18. Systemic production of IL-12 by naked DNA mediated gene transfer: toxicity and attenuation of transgene expression in vivo. Lui, V.W., Falo, L.D., Huang, L. The journal of gene medicine. (2001) [Pubmed]
  19. Immune responses in Eimeria acervulina infected one-day-old broilers compared to amount of Eimeria in the duodenum, measured by real-time PCR. Swinkels, W.J., Post, J., Cornelissen, J.B., Engel, B., Boersma, W.J., Rebel, J.M. Vet. Parasitol. (2006) [Pubmed]
  20. Cystatins up-regulate nitric oxide release from interferon-gamma-activated mouse peritoneal macrophages. Verdot, L., Lalmanach, G., Vercruysse, V., Hartmann, S., Lucius, R., Hoebeke, J., Gauthier, F., Vray, B. J. Biol. Chem. (1996) [Pubmed]
  21. Heteroantibody-mediated cytotoxicity: antibody to the high affinity Fc receptor for IgG mediates cytotoxicity by human monocytes that is enhanced by interferon-gamma and is not blocked by human IgG. Shen, L., Guyre, P.M., Anderson, C.L., Fanger, M.W. J. Immunol. (1986) [Pubmed]
  22. IL-4 and IFN-gamma up-regulate substance P receptor expression in murine peritoneal macrophages. Marriott, I., Bost, K.L. J. Immunol. (2000) [Pubmed]
  23. Coordinate regulation of nitric oxide and 1,25-dihydroxyvitamin D production in the avian myelomonocytic cell line HD-11. Adams, J.S., Ren, S.Y., Arbelle, J.E., Shany, S., Gacad, M.A. Endocrinology (1995) [Pubmed]
  24. Production of interferon-gamma by chicken T cells. Lowenthal, J.W., Digby, M.R., York, J.J. J. Interferon Cytokine Res. (1995) [Pubmed]
  25. GroEL/ES chaperonins protect interferon-gamma against physicochemical stress--study of tertiary structure formation by alpha-casein quenching and ELISA. Vandenbroeck, K., Martens, E., Billiau, A. Eur. J. Biochem. (1998) [Pubmed]
  26. IFN-gamma priming of chicken heterophils upregulates the expression of proinflammatory and Th1 cytokine mRNA following receptor-mediated phagocytosis of Salmonella enterica serovar enteritidis. Kogut, M.H., Rothwell, L., Kaiser, P. J. Interferon Cytokine Res. (2005) [Pubmed]
  27. Immunologic synergism with IL-2 and effects of cCHMIs on mRNA expression of IL-2 and IFN-gamma in chicken peripheral T lymphocyte. Wang, D., Li, X., Xu, L., Hu, Y., Zhang, B., Liu, J. Vaccine (2006) [Pubmed]
  28. Structure of the chicken interferon-gamma gene, and comparison to mammalian homologues. Kaiser, P., Wain, H.M., Rothwell, L. Gene (1998) [Pubmed]
  29. Analysis of chicken cytokine and chemokine gene expression following Eimeria acervulina and Eimeria tenella infections. Hong, Y.H., Lillehoj, H.S., Lee, S.H., Dalloul, R.A., Lillehoj, E.P. Vet. Immunol. Immunopathol. (2006) [Pubmed]
  30. Mouse peritoneal cells confer an antiviral state on mouse cell monolayers: role of interferon. Proietti, E., Gessani, S., Belardelli, F., Gresser, I. J. Virol. (1986) [Pubmed]
  31. Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-gamma. Ribatti, D., Nico, B., Pezzolo, A., Vacca, A., Meazza, R., Cinti, R., Carlini, B., Parodi, F., Pistoia, V., Corrias, M.V. Br. J. Cancer (2006) [Pubmed]
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