Interferon-γ: an overview of signals, mechanisms and functions

Schroder, Kate; Hertzog, Paul J.; Ravasi, Timothy; Hume, David

doi:10.1189/jlb.0603252

Cited by 3,505 publications

(3,204 citation statements)

References 411 publications

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“…Previous studies have shown that IL-26 was produced after viral infection or poly(I:C) stimulation (Fickenscher and Pirzer 2004). Elevated transcript level of IFN-γ was observed in several tissues after LPS or poly(I: C) stimulation, in agreement with studies performed in other vertebrates (Schroder et al 2004;Zou et al 2005).…”

Section: Discussionsupporting

confidence: 88%

“…IL-22 is produced primarily by a subtype of CD4 + T cells, now known as Th17 cells (Dumoutier et al 2000a) while IL-26 mainly by various types of T cells (CD4, CD8, αβ, γδ; Knappe et al 2000). Many aspects of IFN-γ have been elucidated, including the important roles as a potent activator of macrophages and the key regulators in cell-mediated immunity (Schroder et al 2004). In contrast, functions of IL-22 and IL-26 in regulating immune response remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Although functions of these two families have not been fully characterized, their involvement in regulating T cell response is well documented. IFN-γ, a Th1 cytokine, promotes cell-mediated immune response and activates macrophages (Schroder et al 2004) while IL-10 mainly produced by T helper (Th) 2 and T regulatory cells suppresses immune response (Moore et al 2001). are also T-cell-derived cytokines.…”

Section: Introductionmentioning

confidence: 99%

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Comparative study and expression analysis of the interferon gamma gene locus cytokines in Xenopus tropicalis

Nie

2008

Immunogenetics

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Using bioinformatics approach, the genome locus containing interleukin (IL)-22, IL-26, and interferon gamma (IFN-γ) genes has been identified in the amphibian, Xenopus tropicalis. Like that in other vertebrates such as fish, birds, and mammals, the Xenopus IL-22, IL-26, and IFN-γ are clustered in the same chromosome and the adjacent genes are conserved. The genomic structures of the Xenopus IL-22, IL-26, and IFN-γ gene were identical to that of their mammalian counterparts. The Xenopus IL-22 and IL-26 genes contained five exons and four introns while the Xenopus IFN-γ gene consisted of four exons and three introns. The Xenopus IL-22, IL-26, and IFN-γ share 14.1-41.6%, 14.6-31.2%, and 23.7-36.5% identity to their counterparts in other species, respectively. Reversetranscription polymerase chain reaction (PCR) and realtime quantitative PCR analyses revealed that the expression of IL-22, IL-26, and IFN-γ genes was significantly upregulated after simulation with bacterial polyliposaccharide and/or synthetic double-stranded poly(I:C), suggesting these cytokines like those in other vertebrates play an important role in regulating immune response in Xenopus.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative study and expression analysis of the interferon gamma gene locus cytokines in Xenopus tropicalis

Nie

2008

Immunogenetics

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“…We found that Mn 2+ altered the transcript levels of genes that are targets of the IFN-γ signaling pathway (Schroder et al, 2004) and the EGF signaling pathway (Schlessinger, 2004). Twentysix altered genes are known to be the targets of the IFN-γ signaling pathway while 11 are known to be the targets of the EGF signaling pathway (Table 6).…”

Section: The Ifn-γ and Egf Signaling Pathways Might Be Perturbed By Mmentioning

confidence: 89%

Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells

et al. 2007

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Exposure of adult humans to manganese (Mn) has long been known to cause neurotoxicity. Recent evidence also suggests that exposure of children to Mn is associated with developmental neurotoxicity. Astrocytes are critical for the proper functioning of the nervous system, and they play active roles in neurogenesis, synaptogenesis and synaptic neurotransmission. In this report, to help elucidate the molecular events underlying Mn neurotoxicity, we systematically identified the molecular targets of Mn in primary human astrocytes at a genome-wide level, by using microarray gene expression profiling and computational data analysis algorithms. We found that Mn altered the expression of diverse genes ranging from those encoding cytokines and transporters to signal transducers and transcriptional regulators. Particularly, 28 genes encoding proinflammatory chemokines, cytokines and related functions were up-regulated whereas 15 genes encoding functions involved in DNA replication and repair and cell cycle checkpoint control were down-regulated. Consistent with the increased expression of proinflammatory factors, analysis of common regulators revealed that 16 targets known to be positively affected by the interferon-γ signaling pathway were up-regulated by Mn 2+ . In addition, 68 genes were found to be similarly up-or down-regulated by both Mn 2+ and hypoxia. These results from genomic analysis are further supported by data from realtime RT-PCR, Western blotting, flow cytometric and toxicological analyses. Together, these analyses show that Mn 2+ selectively affects cell cycle progression, the expression of hypoxia-responsive genes, and the expression of proinflammatory factors in primary human astrocytes. These results provide important insights into the molecular mechanisms underlying Mn neurotoxicity.

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“…IFN-γ is vital in immune defense against infectious diseases, inflammatory conditions, tumor, and autoimmune diseases. For example, mice lacking either IFN-γ or its receptor have increased susceptibility to the infections of bacterial and viral pathogens [2]. It also regulates various immune responses that are often critical for induction of protective immunity generated by vaccines [1-3].…”

Section: Introductionmentioning

confidence: 99%

Mining of vaccine-associated IFN-γ gene interaction networks using the Vaccine Ontology

et al. 2011

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BackgroundInterferon-gamma (IFN-γ) is vital in vaccine-induced immune defense against bacterial and viral infections and tumor. Our recent study demonstrated the power of a literature-based discovery method in extraction and comparison of the IFN-γ and vaccine-mediated gene interaction networks. The Vaccine Ontology (VO) contains a hierarchy of vaccine names. It is hypothesized that the application of VO will enhance the prediction of IFN-γ and vaccine-mediated gene interaction network.ResultsIn this study, 186 specific vaccine names listed in the Vaccine Ontology (VO) and their semantic relations were used for possible improved retrieval of the IFN-γ and vaccine associated gene interactions. The application of VO allows discovery of 38 more genes and 60 more interactions. Comparison of different layers of IFN-γ networks and the example BCG vaccine-induced subnetwork led to generation of new hypotheses. By analyzing all discovered genes using centrality metrics, 32 genes were ranked high in the VO-based IFN-γ vaccine network using four centrality scores. Furthermore, 28 specific vaccines were found to be associated with these top 32 genes. These specific vaccine-gene associations were further used to generate a network of vaccine-vaccine associations. The BCG and LVS vaccines are found to be the most central vaccines in the vaccine-vaccine association network.ConclusionOur results demonstrate that the combined usages of biomedical ontologies and centrality-based literature mining are able to significantly facilitate discovery of gene interaction networks and gene-concept associations.AvailabilityVO is available at: http://www.violinet.org/vaccineontology; and the SVM edit kernel for gene interaction extraction is available at: http://www.violinet.org/ifngvonet/int_ext_svm.zip

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Interferon-γ: an overview of signals, mechanisms and functions

Cited by 3,505 publications

References 411 publications

Comparative study and expression analysis of the interferon gamma gene locus cytokines in Xenopus tropicalis

Comparative study and expression analysis of the interferon gamma gene locus cytokines in Xenopus tropicalis

Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells

Mining of vaccine-associated IFN-γ gene interaction networks using the Vaccine Ontology

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