Interferon regulatory factor 8 regulates pathways for. Full text interferon kappa is upregulated in psoriasis. The proteins encoded by these genes enhance recognition of the infected cells by the host immune system. This database of interferon regulated genes inte grates information from highthroughput exper iments with annotation, ontology, orthologue sequences from 37 species, tissue expression pat terns and gene regulatory information to enable a detailed investigation of the molecular mecha nisms underlying ifn biology. Therefore, the identification of key genes and pathways is of much importance for clarifying molecular mechanism of hepatocellular carcinoma hcc initiation and progression. Type i ifns are encoded by a family of closely related. Liver cancer is a serious threat to public health and has fairly complicated pathogenesis. Centre for innate immunity and infectious disease interferome v2. Il28b is associated with response to chronic hepatitis c interferon. Isgs play very important roles in innate immunity through a variety of mechanisms.
Interactions among type i and type ii interferon, tumor. Il28b is associated with response to chronic hepatitis c. Genes that were significantly up or down regulated relative to control samples were defined as irgs, annotated and uploaded into the database. Hccassociated gene expression dataset was downloaded from gene expression omnibus database. Definitions interferon regulated genes irgs were identified from multiple microarray and proteomic experiments where cells were treated with ifns. Induction of interferon ifn gene expression leads to increase cellular resistance to viral. Coexpression network analysis reveals the pivotal role of. Finally, ex vivo and in vitro experiments established that ifnbeta. Viruses induce interferonstimulated genes but they also regulate the expression of many hundreds of cellular metabolic and structural genes to facilitate their replication. Interferon ifn cell signaling pathway thermo fisher. In addition, we used the top 500 pm genes for each leprosy state for the analysis of the specific interferon regulated genes. Affymetrix gene chip operating software was used to extract the raw. The interferome and isg databases 11, 12, 3639 were used as sources for. A and c were analyzed using interferome, string and gorilla databases.
Virusinduced transcriptional changes in the brain include. Interferome is an online bioinformatics database of interferonregulated genes irgs. Suppression of ribosomal protein synthesis and protein. Dna microarrays were analyzed by different software, including mas5 affymetrixkegg and gsea gene set enrichment analysis to identify specific pathways both up regulated and down regulated. Celfiles were further processed using the chipster software, version 3. Interferon kappa is upregulated in psoriasis and it upregulates psoriasisassociated cytokines in vivo. Interferome is a database that enables the reliable identification of interferon. Levydifferential viral induction of distinct interferon.
Type i and type ii interferon responses in two human liver. Type i interferonregulated gene expression and signaling. Interferon alfa ifnalpha is an approved therapeutic agent for chronic hepatitis c. Transcriptional dysregulation of interferome in experimental and. Due to the unique features of the chickens immune system, available data from mouse models are not easily transferable. Dynamic expression of interferon lambda regulated genes in primary fibroblasts and immune organs of the chicken. Although hundreds of isgs have been identified, it is commonly recognized that more. A group of proteins, called interferons ifns,1 can directly inhibit viral replication. Irf8 plays an important role in several aspects of myeloid cells, including differentiation. Ifns bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the upregulation of interferonstimulated genes isgs. Regulation of type i interferon gene expression by. This database of interferon regulated genes integrates information from highthroughput experiments with annotation, ontology, orthologue sequences from 37 species, tissue expression patterns and gene regulatory information to enable a detailed investigation of the molecular mechanisms underlying ifn biology. Interactions among type i and type ii interferon, tumor necrosis factor, and.
Article dynamic expression of interferon lambda regulated. This database of interferon regulated genes integrates information from highthroughput. Identification of new type i interferonstimulated genes. Here, we show that expression of key circadian clock genes in the skin is altered by acute inflammation in mice treated topically with the immune activator imiquimod and by chronic inflammation in human psoriatic lesions. Stimulator of interferon genes sting, also known as transmembrane protein 173 tmem173 and mpysmitaeris is a protein that in humans is encoded by the tmem173 gene. Type i interferons are major players against viral infections and mediate their function by the induction of interferon regulated genes irgs. The gene expression profiles of all tissue samples were analyzed based on the platform of the affymetrix human genome u3 plus 2. This database is an upgrade of the original database and contains type i, ii and iii interferon ifn regulated genes. Recently, it became obvious that these cytokines have a multitude of additional functions. Identification of genes differentially regulated by. The parameters were set with 20,900 as total number of genes in the human genome based on data from the ensembl database release 64 and 2,000 as the number of interferonregulated genes as stated in the interferome web site.
Such genes may represent better markers to monitor the effectiveness of ifn therapies, as 25a synthetase and. Dynamic expression of interferon lambda regulated genes in primary fibroblasts and immune organs of the chicken mehboob arslan 1. Protein and dna methylationbased scores as surrogate. Stabilization of ifnar1 improves cytotoxic t lymphocyte survival and suppresses tumor growth. Using interferome searching interferon regulated gene signatures. The data suggests that the repressed expression of interferonstimulated genes may underpin critical aspects of the profibrotic fibroblast phenotype, identifying an area in pulmonary fibrosis that requires further investigation. This database of interferon regulated genes integrates information from high throughput experiments with annotation, ontology, orthologue. Pdf interferome is an open access database of types i, ii and iii interferon regulated genes collected from analysing. Interferon regulated genes irgs were identified from experiments where cells or organisms were treated with an ifn.
Following viral infection, the human body triggers a complex regulatory system of innate and adaptive immune responses designed to defend against these foreign invaders. One of the many responses to the viral invasion is the induction of a family of pleiotropic cytokines known as interferons ifn1. Vastly improved computational infrastructure now enables more complex and faster queries, and supports more data sets from types i. The main functionality of this database is to enable the identification interferon regulated genes in a gene list generated from a highthroughput microarray or proteomic experiment. Quantification of the autoradiographs was performed by densitometry using nih image software version 1. In order to obtain a more comprehensive understanding of the genes regulated by ifns we have used different microarray formats to identify over 400 interferon stimulated genes isg.
Interferonregulated genes are upregulated in the brain following virus infection. To facilitate the dissemination of this data we have compiled a database comprising the. Type ii ifn is represented by a single gene encoding ifn. Although interferon was discovered in chicken cells, details of the response, particularly the identity of hundreds of stimulated genes, are far better described in mammals. Almost as many genes are down regulated suppressed during interferonribavirin treatment as are up regulated. Dynamic expression of interferon lambda regulated genes in. The interferome database was used to identify ifnregulated genes that were upregulated in the brain following infection with jev, wnv, or reovirus. Tissue and time specific expression pattern of interferon. C i d how to find meaningful information interferome v2. A total of 2,834 differentially expressed genes between jdm and hc were identified, including 1,888 downregulated genes and 946 upregulated genes. Enrichment of interferonregulated genes was computed using the hypergeometric test implemented in the r software. Tissue and time specific expression pattern of interferon regulated. We show timeofdaydependent activation of the interferon pathway, a key pathway involved in the host defense response.
To directly characterize the effects of ifnalpha in humans, we used microarrays to profile gene expression in peripheral blood mononuclear cells pbmcs from hepatitis c patients treated with ifnalpha. A database of interferon regulated genes paul hertzog empower eresearch conference sydney 2012 how to find meaningful information. This database of interferon regulated genes integrates information from highthroughput experiments with annotation, ontology, orthologue sequences from 37 species, tissue expression patterns and. This database of interferon regulated genes integrates information from. Type i and type ii interferon responses in two human liver cell lines huh7 and huh6. Ifnregulated genes were identified through the interferome v. Additionally, we found increased expression of interferon ifnregulated genes including ifi27, ifi30, mx1, irf1 and cxcl9 in scc, and to a lower extent in bcc. Virus infection induces the production of type i interferons ifns. This database of ifn regulated genes is an attempt at integrating information from highthroughput experiments to gain a detailed understanding of ifn biology. Gene ontology go term enrichment analysis and kyoto encyclopedia of genes and genomes kegg pathway analysis, based on r software, were. The identification of novel ifnregulated genes in our study may lead to improved therapeutic uses for ifns in different ways. Circadian control of interferonsensitive gene expression.
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