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Gene Review

Ifng  -  interferon gamma

Rattus norvegicus

Synonyms: IFN-gamma, Interferon gamma
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Disease relevance of Ifng

  • Skin lesions in atopic dermatitis (AD) are characterized by hypertrophy of the dermis and epidermis, infiltration by T cells and eosinophils, and expression of the cytokines IL-4, IL-5, and IFN-gamma [1].
  • These results suggest that modulation of specific aspects of the IFN-gamma response may be one mechanism by which trypanosomes overcome host resistance during African trypanosomiasis [2].
  • Oral lipopolysaccharide (LPS) from E. coli and OM-89, an endotoxin free extract containing immunostimulatory glycolipopeptides and heat shock protein (hsp) 65, both downregulated IFN gamma mRNA while only OM-89 in addition suppressed iNOS mRNA and enhanced Th2 cytokine gene expression (p < 0.001) [3].
  • Despite having minimal effects on the acute illness, the IFN-gamma had marked effects on postviral sequelae, the IFN-gamma group having less bronchiolar inflammation (p = 0.025) and fibrosis (p = 0.01), and lacking abnormalities in pulmonary resistance (p = 0.028) and dynamic compliance (p = 0.006) compared with the untreated postviral group [4].
  • In contrast, mice fed with proteins extracted from normal rat, rabbit, and human colon, or from rabbit inflammatory colon, developed severe colitis, with a marked increase in IFNgamma and a decrease in IL10 serum levels, and down-regulation of NK1.1(+) LAL function [5].

High impact information on Ifng

  • T. brucei brucei released a lymphocyte triggering factor (TLTF), which triggered purified CD8+, but not CD4+, T cells to interferon gamma (IFN-gamma) mRNA expression and secretion and to [3H]thymidine incorporation [6].
  • The host-parasite interaction in experimental African trypanosomiasis thus involves parasite release of TLTF, which by binding to CD8 triggers CD8+ cells to produce the parasite growth-promoting cytokine IFN-gamma [6].
  • IFN-gamma provides a growth stimulus for T. brucei brucei, and infected CD8- mice had much lower parasitemia and survived longer than CD8+ mice [6].
  • TNF-alpha was chosen as the transcriptionally inducible target gene to be quantified in alveolar macrophages of control rat lung, as well as low- and high-challenge lungs stimulated by endotoxin and IFN-gamma nebulization [7].
  • Recent studies have shown that gamma-interferon (IFN-gamma) induces the expression of Ia antigen on astrocytes [8].

Chemical compound and disease context of Ifng


Biological context of Ifng

  • Taken together, these results suggest that differential TNF-alpha gene expression in response to LPS and IFN-gamma is strain and cell specific, and reflects both transcriptional and post-transcriptional control mechanisms.(ABSTRACT TRUNCATED AT 400 WORDS)[14]
  • Transient transfection analysis using a rat hepatocyte iNOS promoter-reporter gene plasmid construct showed that IL-1beta-induced promoter activation was abolished in the presence of anti-IFN-gamma or antisense IFN-gamma [15].
  • STAT1 alpha phosphorylation, consistent with IFN gamma-induced signaling, was readily apparent in both cell types, and binding of activated STAT1 alpha from cytoplasmic or nuclear fractions from IFN gamma-treated adult myocytes to a sis-inducible element could be demonstrated by gel-shift assay [16].
  • Additional experiments revealed that the inhibitory activity of GIP-sVSG was associated with reduction in the level of STAT1 phosphorylation, an event required for IFN-gamma-induced macrophage activation [2].
  • CONCLUSION/INTERPRETATION: We hypothesise that the synergistic effect of IL-1beta, TNFalpha and IFNgamma in the functional inhibition and induction of cell death in pancreatic beta cells is signalled through a synergistic activation of mitogen-activated protein kinase activity [17].

Anatomical context of Ifng


Associations of Ifng with chemical compounds


Physical interactions of Ifng


Regulatory relationships of Ifng


Other interactions of Ifng

  • Systemic treatment of nephritic rats with IL-4 reduced NO generation by 40% but did not prevent activation, which is similar to the effect of IL-4 on bone marrow-derived macrophages in vitro when given simultaneously with IFN-gamma [30].
  • Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours [31].
  • In contrast, Ang II did not alter the stimulation of iNOS mRNA levels and NO production elicited by IFN gamma [32].
  • Except for IL-10 and IFN-gamma, all cytokines investigated were induced in the retina, with maximal expression at 22 to 24 hours [33].
  • In hearts rejected by treated recipients, IFN-gamma mRNA did not increase and TGF-beta mRNA was higher [26].

Analytical, diagnostic and therapeutic context of Ifng


  1. Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. Spergel, J.M., Mizoguchi, E., Oettgen, H., Bhan, A.K., Geha, R.S. J. Clin. Invest. (1999) [Pubmed]
  2. Glycosylinositolphosphate soluble variant surface glycoprotein inhibits IFN-gamma-induced nitric oxide production via reduction in STAT1 phosphorylation in African trypanosomiasis. Coller, S.P., Mansfield, J.M., Paulnock, D.M. J. Immunol. (2003) [Pubmed]
  3. Cytokine gene expression in the BB rat pancreas: natural course and impact of bacterial vaccines. Kolb, H., Wörz-Pagenstert, U., Kleemann, R., Rothe, H., Rowsell, P., Scott, F.W. Diabetologia (1996) [Pubmed]
  4. Prevention of chronic postbronchiolitis airway sequelae with IFN-gamma treatment in rats. Sorkness, R.L., Castleman, W.L., Kumar, A., Kaplan, M.R., Lemanske, R.F. Am. J. Respir. Crit. Care Med. (1999) [Pubmed]
  5. Immunomodulation of experimental colitis: the role of NK1.1 liver lymphocytes and surrogate antigens--bystander effect. Shlomai, A., Trop, S., Gotsman, I., Jurim, O., Diment, J., Alper, R., Rabbani, E., Engelhardt, D., Ilan, Y. J. Pathol. (2001) [Pubmed]
  6. CD8 is critically involved in lymphocyte activation by a T. brucei brucei-released molecule. Olsson, T., Bakhiet, M., Höjeberg, B., Ljungdahl, A., Edlund, C., Andersson, G., Ekre, H.P., Fung-Leung, W.P., Mak, T., Wigzell, H. Cell (1993) [Pubmed]
  7. Real-time quantitative RT-PCR after laser-assisted cell picking. Fink, L., Seeger, W., Ermert, L., Hänze, J., Stahl, U., Grimminger, F., Kummer, W., Bohle, R.M. Nat. Med. (1998) [Pubmed]
  8. Viral particles induce Ia antigen expression on astrocytes. Massa, P.T., Dörries, R., ter Meulen, V. Nature (1986) [Pubmed]
  9. Contrasting effects of growth hormone and insulin-like growth factor I on the biological activities of endotoxin in the rat. Liao, W., Rudling, M., Angelin, B. Endocrinology (1997) [Pubmed]
  10. Modulation of tumoricidal activity, induced in bone-marrow-derived mononuclear phagocytes by interferon gamma or Corynebacterium parvum, by interferon beta, tumor necrosis factor, prostaglandin E2, and transforming growth factor beta. Keller, R., Keist, R., van der Meide, P.H. Int. J. Cancer (1991) [Pubmed]
  11. Nepalolide A inhibits the expression of inducible nitric oxide synthase by modulating the degradation of IkappaB-alpha and IkappaB-beta in C6 glioma cells and rat primary astrocytes. Wang, C.N., Shiao, Y.J., Lin, Y.L., Chen, C.F. Br. J. Pharmacol. (1999) [Pubmed]
  12. Neopterin induces nitric oxide-dependent apoptosis in rat vascular smooth muscle cells. Hoffmann, G., Kenn, S., Wirleitner, B., Deetjen, C., Frede, S., Smolny, M., Rieder, J., Fuchs, D., Baier-Bitterlich, G., Schobersberger, W. Immunobiology (1998) [Pubmed]
  13. c-Jun N-terminal kinase inhibition and alpha-tocopherol protect midbrain dopaminergic neurons from interferon-gamma/lipopolysaccharide-induced injury without affecting nitric oxide production. Shibata, H., Katsuki, H., Okawara, M., Kume, T., Akaike, A. J. Neurosci. Res. (2006) [Pubmed]
  14. Differential tumor necrosis factor alpha expression by astrocytes from experimental allergic encephalomyelitis-susceptible and -resistant rat strains. Chung, I.Y., Norris, J.G., Benveniste, E.N. J. Exp. Med. (1991) [Pubmed]
  15. Interleukin 1beta-stimulated production of nitric oxide in rat hepatocytes is mediated through endogenous synthesis of interferon gamma. Schroeder, R.A., Gu, J.S., Kuo, P.C. Hepatology (1998) [Pubmed]
  16. Regulation of cytokine-inducible nitric oxide synthase in cardiac myocytes and microvascular endothelial cells. Role of extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and STAT1 alpha. Singh, K., Balligand, J.L., Fischer, T.A., Smith, T.W., Kelly, R.A. J. Biol. Chem. (1996) [Pubmed]
  17. TNFalpha and IFNgamma potentiate IL-1beta induced mitogen activated protein kinase activity in rat pancreatic islets of Langerhans. Andersen, N.A., Larsen, C.M., Mandrup-Poulsen, T. Diabetologia (2000) [Pubmed]
  18. Role of poly-ADP ribosyltransferase activation in the vascular contractile and energetic failure elicited by exogenous and endogenous nitric oxide and peroxynitrite. Szabó, C., Zingarelli, B., Salzman, A.L. Circ. Res. (1996) [Pubmed]
  19. Double-stranded RNA inhibits beta-cell function and induces islet damage by stimulating beta-cell production of nitric oxide. Heitmeier, M.R., Scarim, A.L., Corbett, J.A. J. Biol. Chem. (1999) [Pubmed]
  20. Inducible nitric oxide synthase in rat hepatic lipocytes and the effect of nitric oxide on lipocyte contractility. Rockey, D.C., Chung, J.J. J. Clin. Invest. (1995) [Pubmed]
  21. Nitric oxide prevents tumor necrosis factor alpha-induced rat hepatocyte apoptosis by the interruption of mitochondrial apoptotic signaling through S-nitrosylation of caspase-8. Kim, Y.M., Kim, T.H., Chung, H.T., Talanian, R.V., Yin, X.M., Billiar, T.R. Hepatology (2000) [Pubmed]
  22. Transforming growth factors type beta 1 and beta 2 suppress rat astrocyte autoantigen presentation and antagonize hyperinduction of class II major histocompatibility complex antigen expression by interferon-gamma and tumor necrosis factor-alpha. Schluesener, H.J. J. Neuroimmunol. (1990) [Pubmed]
  23. Synergistic stimulation of MHC class I and IRF-1 gene expression by IFN-gamma and TNF-alpha in oligodendrocytes. Agresti, C., Bernardo, A., Del Russo, N., Marziali, G., Battistini, A., Aloisi, F., Levi, G., Coccia, E.M. Eur. J. Neurosci. (1998) [Pubmed]
  24. Tumor necrosis factor-alpha and interferon-gamma suppress both gene expression and deoxyribonucleic acid-binding of TTF-2 in FRTL-5 cells. Miyazaki, A., Shimura, H., Endo, T., Haraguchi, K., Onaya, T. Endocrinology (1999) [Pubmed]
  25. Regulation of the rat liver sodium-dependent bile acid cotransporter gene by prolactin. Mediation of transcriptional activation by Stat5. Ganguly, T.C., O'Brien, M.L., Karpen, S.J., Hyde, J.F., Suchy, F.J., Vore, M. J. Clin. Invest. (1997) [Pubmed]
  26. Long-term survival of hamster-to-rat cardiac xenografts in the absence of a Th2 shift. Brouard, S., Blancho, G., Moreau, A., Heslan, J.M., Cuturi, M.C., Soulillou, J.P. Transplantation (1998) [Pubmed]
  27. Generation of rat Th2-like cells in vitro is interleukin-4-dependent and inhibited by interferon-gamma. Noble, A., Staynov, D.Z., Kemeny, D.M. Immunology (1993) [Pubmed]
  28. Dysregulated luminal bacterial antigen-specific T-cell responses and antigen-presenting cell function in HLA-B27 transgenic rats with chronic colitis. Qian, B.F., Tonkonogy, S.L., Hoentjen, F., Dieleman, L.A., Sartor, R.B. Immunology (2005) [Pubmed]
  29. Anti-inflammatory roles of retinoic acid in rat brain astrocytes: Suppression of interferon-gamma-induced JAK/STAT phosphorylation. Choi, W.H., Ji, K.A., Jeon, S.B., Yang, M.S., Kim, H., Min, K.J., Shong, M., Jou, I., Joe, E.H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  30. Macrophages from inflamed but not normal glomeruli are unresponsive to anti-inflammatory cytokines. Erwig, L.P., Stewart, K., Rees, A.J. Am. J. Pathol. (2000) [Pubmed]
  31. Cytokine mRNA expression in postischemic/reperfused myocardium. Herskowitz, A., Choi, S., Ansari, A.A., Wesselingh, S. Am. J. Pathol. (1995) [Pubmed]
  32. Cytokine- and endotoxin-induced nitric oxide synthase in rat astroglial cultures: differential modulation by angiotensin II. Kopnisky, K.L., Sumners, C., Chandler, L.J. J. Neurochem. (1997) [Pubmed]
  33. Expression of multiple cytokines and IL-1RA in the uvea and retina during endotoxin-induced uveitis in the rat. de Vos, A.F., Klaren, V.N., Kijlstra, A. Invest. Ophthalmol. Vis. Sci. (1994) [Pubmed]
  34. Peroxynitrite formation during rat hepatic allograft rejection. Yamaguchi, Y., Okabe, K., Matsumura, F., Akizuki, E., Matsuda, T., Ohshiro, H., Liang, J., Yamada, S., Mori, K., Ogawa, M. Hepatology (1999) [Pubmed]
  35. Intragraft cytokine expression and tolerance induction in rat renal allografts. Saggi, B.H., Fisher, R.A., Bu, D., Tawes, J.W., Riley, R., Posner, M.P. Transplantation (1999) [Pubmed]
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