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Gene Review

IFNG  -  interferon, gamma

Bos taurus

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Disease relevance of IFNG

  • Biologically active bovine IFN-gamma was synthesized in an Escherichia coli expression system [1].
  • CONCLUSIONS: In GCA, IFN-gamma functional polymorphisms are associated with clinical manifestations of severity rather than susceptibility to this vasculitis [2].
  • Enhancement of a secondary antibody response to vesicular stomatitis virus "G" protein by IFN-gamma treatment at primary immunization [3].
  • Together, these results are consistent with a protective role of IFN-gamma during the heterologous response against influenza virus independently of the generation and local recruitment of cross-reactive CTLs [4].
  • We assessed the contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68 (H3N2) virus [4].

High impact information on IFNG

  • Interferon gamma (IFN-gamma) is the most potent inducer of class II major histocompatibility complex (MHC) genes [5].
  • Transfection of YB-1 by this procedure resulted in the near abrogation of IFN-gamma induced HLA-DR antigen and mRNA expression [5].
  • In contrast to murine macrophages, IFN-gamma inhibited TNF-alpha-stimulated induction of endothelial NO synthase activity in a concentration-dependent manner [6].
  • This observation suggests that there is major difference in the response of BAEC and murine macrophages to IFN-gamma [6].
  • Ex vivo, draining lymph node cells from CBD-treated mice showed a diminished CII-specific proliferation and IFN-gamma production, as well as a decreased release of tumor necrosis factor by knee synovial cells [7].

Chemical compound and disease context of IFNG

  • We have investigated the effects of IFN-gamma treatment on a neutralizing antibody response to vesicular stomatitis virus (VSV) when administered in conjunction with immunization using purified envelope glycoprotein "G" of VSV [3].
  • Cattle undergoing initial infection with the rickettsia Anaplasma marginale were treated with either a monoclonal antibody (MoAb) with neutralizing activity for bovine interferon gamma (IFN-gamma) or aminoguanidine (AG), a specific inhibitor of the inducible form of nitric oxide synthetase (iNOS) [8].
  • Heat-killed Listeria monocytogenes induced more iNOS mRNA and nitrite than IFN-gamma, but much less than L. mono-cytogenes and IFN-gamma combined [9].
  • Live and gamma-irradiated-killed Brucella abortus strain 2308 increased interleukin 1 (IL-1), but not interleukin 2 (IL-2), interferon-gamma (IFN-gamma), or prostaglandin E2 (PGE2) production when incubated with normal bovine peripheral blood mononuclear cells (PBMC) [10].
  • Cells from cows with subclinical paratuberculosis produced significantly more TNF and IFN-gamma in response to MpS than cells from the other 2 groups [11].

Biological context of IFNG


Anatomical context of IFNG

  • In the first experiment, RT-PCR revealed the presence of INDO mRNA in luteal cells treated with IFNG, but not in untreated cells [13].
  • These findings suggest that endothelial cell expression of vasoactive mediators is modified by the temporal interplay of at least two immune mediators, IFN-gamma and TNF-alpha [6].
  • However, anti-FKN mAb did not affect the production of either serum anti-collagen type II (CII) IgG or IFN-gamma by CII-stimulated splenic T cells [14].
  • Cytolysis of IgSV195 cells by SV40 T-antigen-specific H-2b-restricted lymphocytes is similarly dependent on IFN-gamma pretreatment [15].
  • Using specific antibodies, we have confirmed that extracellular signal-regulated kinases and p38 MAP kinase were activated by LPS and IFN-gamma in retinal pigmented epithelial cells [16].

Associations of IFNG with chemical compounds


Regulatory relationships of IFNG


Other interactions of IFNG

  • There was an early increase in transcripts for genes encoding proinflammatory mediators (IFNG, IL1A, TNF, and IL12) in N'Dama by 14 days postinfection (dpi) compared with preinfection levels that was not detected in the susceptible Boran breed [21].
  • However, NO production induced by TLR2 or TLR4 agonists was strongly modulated either by IFN-gamma costimulation or BVDV preinfection [22].
  • However, similar experiments revealed that the activation of interferon regulatory factor-1 (IRF-1) by LPS/IFN-gamma was decreased by IFN-alpha [18].
  • Stereoselective inhibitors of NOS and cycloheximide inhibited LPS-IFN-gamma-induced nitrite release in both cells, whereas transforming growth factor-beta (TGF-beta) slightly potentiated it [23].
  • We previously demonstrated that iNOS can be induced in cultured bovine monocytes in response to IFN-gamma and TNF-alpha but lose this capability in a short period of time [24].

Analytical, diagnostic and therapeutic context of IFNG

  • Mapping of the interferon gamma (IFNG) gene in river and swamp buffaloes by in situ hybridization [25].
  • Analysis by Western and Northern blots showed that RPE cells co-stimulated with IFN-alpha or IFN-beta with LPS/IFN-gamma accumulated lower levels of NOS-2 protein and mRNA than in the presence of LPS/IFN-gamma alone [18].
  • Analysis of NF-kappaB activation by electrophoretic mobility shift assay demonstrated that LPS/IFN-gamma-induced NF-kappaB binding was not changed by the presence of IFN-alpha [18].
  • IFN-gamma treatment in conjunction with a single primary immunization may therefore provide a practical means of enhancing protection from a viral challenge without the use of inflammatory adjuvants or booster immunizations [3].
  • Our study strongly implies that CD8+ T cells that proliferate and produce IFN-gamma in response to the exogenous Ag would play a vital role in Ag-specific immunosuppression [26].


  1. Cloning, sequence, and expression of bovine interferon-gamma. Cerretti, D.P., McKereghan, K., Larsen, A., Cosman, D., Gillis, S., Baker, P.E. J. Immunol. (1986) [Pubmed]
  2. Interferon-gamma gene microsatellite polymorphisms in patients with biopsy-proven giant cell arteritis and isolated polymyalgia rheumatica. Gonzalez-Gay, M.A., Hajeer, A.H., Dababneh, A., Garcia-Porrua, C., Amoli, M.M., Llorca, J., Ollier, W.E. Clinical and experimental rheumatology. (2004) [Pubmed]
  3. Enhancement of a secondary antibody response to vesicular stomatitis virus "G" protein by IFN-gamma treatment at primary immunization. Anderson, K.P., Fennie, E.H., Yilma, T. J. Immunol. (1988) [Pubmed]
  4. Protective role of gamma interferon during the recall response to influenza virus. Bot, A., Bot, S., Bona, C.A. J. Virol. (1998) [Pubmed]
  5. YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes. Ting, J.P., Painter, A., Zeleznik-Le, N.J., MacDonald, G., Moore, T.M., Brown, A., Schwartz, B.D. J. Exp. Med. (1994) [Pubmed]
  6. Effects of interferon-gamma on nitric oxide synthase activity and endothelin-1 production by vascular endothelial cells. Lamas, S., Michel, T., Collins, T., Brenner, B.M., Marsden, P.A. J. Clin. Invest. (1992) [Pubmed]
  7. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Malfait, A.M., Gallily, R., Sumariwalla, P.F., Malik, A.S., Andreakos, E., Mechoulam, R., Feldmann, M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. Anaplasma marginale: effect of the treatment of cattle with an interferon gamma-neutralizing monoclonal antibody or the nitric oxide synthetase inhibitor aminoguanidine on the course of infection. Gale, K.R., Leatch, G., Dimmock, C.M., Wood, P.R. Parasite Immunol. (1997) [Pubmed]
  9. Induction of nitric oxide synthase in bovine mononuclear phagocytes is differentiation stage-dependent. Jungi, T.W., Thöny, M., Brcic, M., Adler, B., Pauli, U., Peterhans, E. Immunobiology (1996) [Pubmed]
  10. In vitro effects of live and killed Brucella abortus on bovine cytokine and prostaglandin E2 production. Stevens, M.G., Olsen, S.C. Vet. Immunol. Immunopathol. (1994) [Pubmed]
  11. Cytokine secretion by peripheral blood mononuclear cells from cows infected with Mycobacterium paratuberculosis. Stabel, J.R. Am. J. Vet. Res. (2000) [Pubmed]
  12. A comprehensive survey for polymorphisms in the bovine IFN-gamma gene reveals a highly polymorphic intronic DNA sequence allowing improved genotyping of Bovinae. Schmidt, P., Kühn, C., Maillard, J.C., Pitra, C., Tiemann, U., Weikard, R., Schwerin, M. J. Interferon Cytokine Res. (2002) [Pubmed]
  13. Indoleamine 2,3-dioxygenase participates in the interferon-gamma-induced cell death process in cultured bovine luteal cells. Cannon, M.J., Pate, J.L. Biol. Reprod. (2006) [Pubmed]
  14. Inhibition of fractalkine ameliorates murine collagen-induced arthritis. Nanki, T., Urasaki, Y., Imai, T., Nishimura, M., Muramoto, K., Kubota, T., Miyasaka, N. J. Immunol. (2004) [Pubmed]
  15. Functional pancreatic beta-cell line from SV40 T-antigen transgenic mouse. Gilligan, A., Jewett, L., Simon, D., Damjanov, I., Matschinsky, F.M., Weik, H., Pinkert, C., Knowles, B.B. Diabetes (1989) [Pubmed]
  16. Role of interferon regulatory factor-1 and mitogen-activated protein kinase pathways in the induction of nitric oxide synthase-2 in retinal pigmented epithelial cells. Faure, V., Hecquet, C., Courtois, Y., Goureau, O. J. Biol. Chem. (1999) [Pubmed]
  17. Differential regulation of L-arginine transport and nitric oxide production by vascular smooth muscle and endothelium. Durante, W., Liao, L., Iftikhar, I., O'Brien, W.E., Schafer, A.I. Circ. Res. (1996) [Pubmed]
  18. Inhibition of inducible nitric oxide synthase expression by interferons alpha and beta in bovine retinal pigmented epithelial cells. Faure, V., Courtois, Y., Goureau, O. J. Biol. Chem. (1997) [Pubmed]
  19. CD80 and CD86, but not CD154, augment DNA vaccine-induced protection in experimental bovine tuberculosis. Maue, A.C., Waters, W.R., Palmer, M.V., Whipple, D.L., Minion, F.C., Brown, W.C., Estes, D.M. Vaccine (2004) [Pubmed]
  20. IL-4 and IL-10 inhibition of IFN-gamma- and TNF-alpha-dependent nitric oxide production from bovine mononuclear phagocytes exposed to Babesia bovis merozoites. Goff, W.L., Johnson, W.C., Parish, S.M., Barrington, G.M., Elsasser, T.H., Davis, W.C., Valdez, R.A. Vet. Immunol. Immunopathol. (2002) [Pubmed]
  21. Cytokine mRNA profiling of peripheral blood mononuclear cells from trypanotolerant and trypanosusceptible cattle infected with Trypanosoma congolense. O'Gorman, G.M., Park, S.D., Hill, E.W., Meade, K.G., Mitchell, L.C., Agaba, M., Gibson, J.P., Hanotte, O., Naessens, J., Kemp, S.J., MacHugh, D.E. Physiol. Genomics (2006) [Pubmed]
  22. Evidence for dissociation of TLR mRNA expression and TLR agonist-mediated functions in bovine macrophages. Franchini, M., Schweizer, M., Mätzener, P., Magkouras, I., Sauter, K.S., Mirkovitch, J., Peterhans, E., Jungi, T.W. Vet. Immunol. Immunopathol. (2006) [Pubmed]
  23. Expression of inducible nitric oxide synthase in bovine corneal endothelial cells and keratocytes in vitro after lipopolysaccharide and cytokines stimulation. Dighiero, P., Behar-Cohen, F., Courtois, Y., Goureau, O. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  24. The role of IL-10 in iNOS and cytokine mRNA expression during in vitro differentiation of bovine mononuclear phagocytes. Goff, W.L., O'Rourke, K.I., Johnson, W.C., Lacy, P.A., Davis, W.C., Wyatt, C.R. J. Interferon Cytokine Res. (1998) [Pubmed]
  25. Mapping of the interferon gamma (IFNG) gene in river and swamp buffaloes by in situ hybridization. Hassanane, M.S., Chowdhary, B.P., Gu, F., Andersson, L., Gustavsson, I. Hereditas (1994) [Pubmed]
  26. CD8+ T cells specific to the exogenous antigen. Mode of antigen recognition and possible implication in immunosuppression. Hisatsune, T., Nishijima, K., Kohyama, M., Kato, H., Kaminogawa, S. J. Immunol. (1995) [Pubmed]
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