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

• 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 [11].
• Nitric oxide inhibits Marek's disease virus replication but is not the single decisive factor in interferon-gamma-mediated viral inhibition [12].
• Body weight gain, fecal oocyst shedding, concentrations of plasma NO2- + NO3-, carotenoid, and interferon-gamma were measured at two different time periods postinfection [13].
• A rabbit serum made to a synthetic peptide of IFN-gamma immunoprecipitated a 60 kDa E. coli maltose-binding fusion protein of recombinant IFN-gamma (MBP-IFN) and a 26-27 kDa secreted protein from COS cells and Con A-activated spleen cells [14].
• Inhibition of interferon-gamma production from lymphocytes stimulated with food antigens by a beta 2-agonist, procaterol, in patients with food-sensitive atopic dermatitis [15].

Biological context of IFNG

• Accordingly, IRF-10 is involved in the upregulation of two primary IFN-gamma target genes (major histocompatibility complex [MHC] class I and guanylate-binding protein) and interferes with the induction of the type I IFN target gene for 2',5'-oligo(A) synthetase [8].
• Similarly, DEX significantly reduced the IFN-gamma stimulation of ADCC and phagocytosis [16].
• We also studied effects of IFN-gamma and the synthetic glucocorticoid dexamethasone (DEX) on antibody-dependent cytotoxicity (ADCC) of chicken erythrocytes and phagocytosis of IgG-coated ox RBC by human PMN [16].
• The phosphorylation of STAT1 by interferon-gamma was also inhibited by CdCl2 [17].
• The transgene attenuation effect of IL-12 pre-dosing (either by IL-12 or rmIL-12), mediated by IFN-gamma, provided important insights for the design of IL-12 combination gene therapy and the improvement of gene vectors for IL-12 therapy [18].

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].

References