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

• The open reading frame predicts that the bovine IFN-gamma precursor is composed of 166 amino acids with a predicted m.w. of 19,393 [1].
• Bovine interferon-gamma (IFN-gamma) sequences have been isolated by screening a cDNA library with a human IFN-gamma cDNA probe [1].
• Alignment of the amino acid sequence with human IFN-gamma indicates that mature bovine IFN-gamma is composed of 143 amino acids with a predicted m.w. of 16,858 [1].
• The BoIFNG DNA sequence conforms to the published part of Bo-IFN-gamma cDNA [12].
• Single-cell gel electrophoresis and microscopic image analysis revealed that 1-MT inhibited DNA fragmentation induced by IFNG [13].

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

• Evidence supporting the involvement of an IFNG-inducible enzymatic pathway that degrades tryptophan in IFNG-induced death of bovine luteal cells is presented in this study [13].
• To determine whether INDO participates in IFNG-induced death of bovine luteal cells, an experiment was performed to test the effect of 1-methyl-D-tryptophan (1-MT), an inhibitor of INDO, on IFNG-induced DNA fragmentation in luteal cells [13].
• In murine macrophages IFN-gamma synergizes with TNF-alpha or lipopolysaccharide to induce robust increases in calcium-independent NO synthase activity [6].
• Exposure of BASMCs to interferon gamma (IFN-gamma) or lipopolysaccharide (LPS) also stimulated NO release but did not affect L-arginine transport [17].
• These types of interferons did not aid LPS in the production of nitrite, but markedly inhibited in a concentration-dependent manner the nitrite release due to LPS/IFN-gamma [18].

Regulatory relationships of IFNG

• Co-administration of either CD80/CD86 or CD154 enhanced ESAT-6-specific IFN-gamma responses as compared to animals vaccinated with ESAT-6 DNA alone [19].
• However, while merozoites plus IFN-gamma induced TNF-alpha mRNA expression in MDM, NO was not produced [20].
• Analysis by reverse transcriptase-polymerase chain reaction, Western blot, and electrophoretic mobility shift assay demonstrated that IFN-gamma alone or combined with LPS induced an accumulation of IRF-1 mRNA and protein and IRF-1 DNA binding [16].

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].

References