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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/28318807/microrna-302d-targets-irf9-to-regulate-the-ifn-induced-gene-expression-in-sle
#1
Siobhán Smith, Thilini Fernando, Pei Wen Wu, Jane Seo, Joan Ní Gabhann, Olga Piskareva, Eoghan McCarthy, Donough Howard, Paul O'Connell, Richard Conway, Phil Gallagher, Eamonn Molloy, Raymond L Stallings, Grainne Kearns, Lindsy Forbess, Mariko Ishimori, Swamy Venuturupalli, Daniel Wallace, Michael Weisman, Caroline A Jefferies
Systemic lupus erythematosus (SLE) is a complex disease targeting multiple organs as a result of overactivation of the type I interferon (IFN) system, a feature currently being targeted by multiple biologic therapies against IFN-α. We have identified an estrogen-regulated microRNA, miR-302d, whose expression is decreased in SLE patient monocytes and identify its target as interferon regulatory factor (IRF)-9, a critical component of the transcriptional complex that regulates expression of interferon-stimulated genes (ISGs)...
March 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28316371/znf395-is-an-activator-of-a-subset-of-ifn-stimulated-genes
#2
Linda Schroeder, Christine Herwartz, Darko Jordanovski, Gertrud Steger
Activation of the interferon (IFN) pathway in response to infection with pathogens results in the induction of IFN-stimulated genes (ISGs) including proinflammatory cytokines, which mount the proper antiviral immune response. However, aberrant expression of these genes is pathogenic to the host. In addition to IFN-induced transcription factors non-IFN-regulated factors contribute to the transcriptional control of ISGs. Here, we show by genome wide expression analysis, siRNA-mediated suppression and Doxycycline-induced overexpression that the cellular transcription factor ZNF395 activates a subset of ISGs including the chemokines CXCL10 and CXCL11 in keratinocytes...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28302626/sting-irf3-triggers-endothelial-inflammation-in-response-to-free-fatty-acid-induced-mitochondrial-damage-in-diet-induced-obesity
#3
Yun Mao, Wei Luo, Lin Zhang, Weiwei Wu, Liangshuai Yuan, Hao Xu, Juhee Song, Keigi Fujiwara, Jun-Ichi Abe, Scott A LeMaire, Xing Li Wang, Ying H Shen
OBJECTIVE: Metabolic stress in obesity induces endothelial inflammation and activation, which initiates adipose tissue inflammation, insulin resistance, and cardiovascular diseases. However, the mechanisms underlying endothelial inflammation induction are not completely understood. Stimulator of interferon genes (STING) is an important molecule in immunity and inflammation. In the present study, we sought to determine the role of STING in palmitic acid-induced endothelial activation/inflammation...
March 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28299025/interleukin-28b-rs12979860-c-t-polymorphism-and-acute-cellular-rejection-after-liver-transplantation
#4
H Fereidooni, N Azarpira, R Yaghobi, A Vahdati, S A Malek-Hoseini
BACKGROUND: Interleukin-28 (IL-28B) rs12979860 C/T polymorphism is a known predictor of sustained virological response after antiviral treatment in hepatitis C. IL-28B affects the innate immune system as well as intrahepatic expression level of interferon-stimulated genes. OBJECTIVE: To investigate the effect of recipient IL-28B polymorphism on occurrence of acute rejection after liver transplantation. METHODS: 140 liver allograft recipients were selected...
2017: International Journal of Organ Transplantation Medicine
https://www.readbyqxmd.com/read/28295457/hepatic-ifit3-predicts-interferon-%C3%AE-therapeutic-response-in-patients-of-hepatocellular-carcinoma
#5
Yingyun Yang, Ye Zhou, Jin Hou, Chunmei Bai, Zhenyang Li, Jia Fan, Irene O L Ng, Weiping Zhou, Huichuan Sun, Qiongzhu Dong, Joyce M F Lee, Chung-Mau Lo, Kwan Man, Yun Yang, Nan Li, Guoshan Ding, Yizhi Yu, Xuetao Cao
Adjuvant interferon-α (IFN-α) therapy is used to control certain types of cancer in clinics. For hepatocellular carcinoma (HCC), IFN-α therapy is effective in only a subgroup of HCC patients, therefore identifying biomarkers to predict the response to IFN-α therapy is of high significance and clinical utility. As the induced IFN-stimulated genes (ISGs) expression following IFN-α treatment plays pivotal roles in IFN-α effects, we screened ISGs expression in HCC tissues and found several ISGs were significantly decreased in HCC...
March 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28293236/interferon-lambda-modulating-immunity-in-infectious-diseases
#6
REVIEW
Mohammedyaseen Syedbasha, Adrian Egli
Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28289145/irf6-promotes-keratinocyte-differentiation-in-response-to-porphyromonas-gingivalis
#7
Jennifer Huynh, Glen M Scholz, Jiamin Aw, Eric C Reynolds
We recently demonstrated that the expression of the Interferon regulatory factor 6 (IRF6) transcription factor in oral keratinocytes was stimulated by the periodontal pathogen Porphyromonas gingivalis Here, we have established that IRF6 promotes the differentiation of oral keratinocytes in response to P. gingivalis This was evidenced by the IRF6-dependent upregulation of specific markers of keratinocyte terminal differentiation (e.g. Involucrin, IVL; Keratin 13, KRT13), together with additional transcriptional regulators of keratinocyte differentiation, including Grainyhead-like 3 (GRHL3) and Ovo-like zinc finger 1 (OVOL1)...
March 13, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28289093/a-hot-spot-on-interferon-alpha-beta-receptor-subunit-1-ifnar1-underpins-its-interaction-with-interferon-%C3%AE-and-dictates-signaling
#8
Nicole A de Weerd, Antony Y Matthews, Phillip R Pattie, Nollaig M Bourke, San S Lim, Julian P Vivian, Jamie Rossjohn, Paul J Hertzog
The interaction of IFN-β with its receptor IFNAR1 is vital for host-protective anti-viral and anti-proliferative responses, but signaling via this interaction can be detrimental if dysregulated. While it is established that IFNAR1 is an essential component of the IFNAR signaling complex, the key residues underpinning the IFN-β-IFNAR1 interaction are unknown. Guided by the crystal structure of the IFN-β-IFNAR1 complex, we used truncation variants and site directed mutagenesis to investigate domains and residues enabling complexation of IFN-β to IFNAR1...
March 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28288457/interferon-dependent-induction-of-clr-b-during-mouse-cytomegalovirus-infection-protects-bystander-cells-from-natural-killer-cells-via-nkr-p1b-mediated-inhibition
#9
Christina L Kirkham, Oscar A Aguilar, Tao Yu, Miho Tanaka, Aruz Mesci, Kuan-Lun Chu, Jason H Fine, Karen L Mossman, Rod Bremner, David S J Allan, James R Carlyle
Natural killer (NK) cells are innate lymphocytes that aid in self-nonself discrimination by recognizing cells undergoing pathological alterations. The NKR-P1B inhibitory receptor recognizes Clr-b, a self-encoded marker of cell health downregulated during viral infection. Here, we show that Clr-b loss during mouse cytomegalovirus (MCMV) infection is predicated by a loss of Clr-b (Clec2d) promoter activity and nascent transcripts, driven in part by MCMV ie3 (M122) activity. In contrast, uninfected bystander cells near MCMV-infected fibroblasts reciprocally upregulate Clr-b expression due to paracrine type-I interferon (IFN) signaling...
March 14, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28288101/opposing-macrophage-polarization-programs-show-extensive-epigenomic-and-transcriptional-cross-talk
#10
Viviana Piccolo, Alessia Curina, Marco Genua, Serena Ghisletti, Marta Simonatto, Arianna Sabò, Bruno Amati, Renato Ostuni, Gioacchino Natoli
Stimulation of macrophages with interferon-γ (IFN-γ) and interleukin 4 (IL-4) triggers distinct and opposing activation programs. During mixed infections or cancer, macrophages are often exposed to both cytokines, but how these two programs influence each other remains unclear. We found that IFN-γ and IL-4 mutually inhibited the epigenomic and transcriptional changes induced by each cytokine alone. Computational and functional analyses revealed the genomic bases for gene-specific cross-repression. For instance, while binding motifs for the transcription factors STAT1 and IRF1 were associated with robust and IL-4-resistant responses to IFN-γ, their coexistence with binding sites for auxiliary transcription factors such as AP-1 generated vulnerability to IL-4-mediated inhibition...
March 13, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28286505/mda5-induces-a-stronger-interferon-response-than-rig-i-to-gcrv-infection-through-a-mechanism-involving-the-phosphorylation-and-dimerization-of-irf3-and-irf7-in-cik-cells
#11
Quanyuan Wan, Chunrong Yang, Youliang Rao, Zhiwei Liao, Jianguo Su
Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are critical cytosolic sensors that trigger the production of interferons (IFNs). Though their recognition functions are well identified, their unique roles in the downstream signal transduction remain to be elucidated. Herein, we report the differential effect between grass carp (Ctenopharyngodon idella) MDA5 (CiMDA5) and CiRIG-I on the production of various IFNs upon grass carp reovirus (GCRV) infection in C. idella kidney (CIK) cell line...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28285335/cell-type-dependent-regulation-of-free-isg15-levels-and-isgylation
#12
Angeles C Tecalco Cruz, Karen Mejía-Barreto
Interferon-stimulated gene 15 (ISG15) is an ubiquitin-like protein, which can either be found as a free protein or covalently-bound to target proteins via ISGylation. The functions of free and conjugated ISG15 are ambiguous in tumorigenesis owing to its roles as an oncogene and a tumour suppressor gene. This dual role for ISG15 could be a result of the cancer cell type and the cellular context. Here, we report that ISG15 expression is upregulated in different cancer cells compared to normal cells. Furthermore, we found higher endogenous, free ISG15 protein levels in MCF7 breast cancer cells than in other cells, suggesting that non-conjugated ISG15 levels are cell type-specific...
March 11, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28284594/orally-administered-live-attenuated-salmonella-typhimurium-protects-mice-against-lethal-infection-with-h1n1-influenza-virus
#13
Nitin Machindra Kamble, Irshad Ahmed Hajam, John Hwa Lee
Pre-stimulation of toll-like receptors (TLRs) by agonists has been shown to increase protection against influenza virus infection. In this study, we evaluated the protective response generated against influenza A/Puerto Rico/8/1934 (PR8; H1N1) virus by oral and nasal administration of live attenuated Salmonella enterica serovar Typhimurium, JOL911 strain, in mice. Oral and nasal inoculation of JOL911 significantly increased the mRNA copy number of TLR-2, TLR4 and TLR5, and downstream type I interferon (IFN) molecules, IFN-α and IFN-β, both in peripheral blood mononuclear cells (PBMCs) and in lung tissue...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28281905/implications-of-toll-like-receptors-in-ebola-infection
#14
Amene Saghazadeh, Nima Rezaei
The potential roles of toll-like receptors (TLRs) in immunopathogenesis of Ebola virus disease should be unraveled to provoke possible prophylactic or therapeutic implications of TLRs for EVD. Areas covered: The Ebola virus (EBOV) infection virtually paralyses all the main mechanisms responsible for induction of type I interferon (IFN-I) response. To summarize, EBOV infection interferes with: a) the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway that is mediated by TLR3 and TLR4 signaling; b) the interferon regulatory factor 7 (IRF7) pathway that is stimulated by TLR7 and TLR9; c) the intracellular signaling that is induced by retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs); and d) the autocrine/paracrine feedback loop that is mediated by the IFN-stimulated gene factor 3 (ISGF3) complex...
April 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28281680/human-endometrial-stromal-cells-are-highly-permissive-to-productive-infection-by-zika-virus
#15
Isabel Pagani, Silvia Ghezzi, Adele Ulisse, Alicia Rubio, Filippo Turrini, Elisabetta Garavaglia, Massimo Candiani, Concetta Castilletti, Giuseppe Ippolito, Guido Poli, Vania Broccoli, Paola Panina-Bordignon, Elisa Vicenzi
Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted to humans by mosquito bites but also from mother to fetus and by sexual intercourse. We here show that primary human endometrial stromal cells (HESC) are highly permissive to ZIKV infection and support its in vitro replication. ZIKV envelope expression was detected in the endoplasmic reticulum whereas double-stranded viral RNA colocalized with vimentin filaments to the perinuclear region. ZIKV productive infection also occurred in the human T-HESC cell line together with the induction of interferon-β (IFN-β) and of IFN-stimulated genes...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28279982/a-prosurvival-dna-damage-induced-cytoplasmic-interferon-response-is-mediated-by-end-resection-factors-and-is-limited-by-trex1
#16
Erkin Erdal, Syed Haider, Jan Rehwinkel, Adrian L Harris, Peter J McHugh
Radiotherapy and chemotherapy are effective treatment methods for many types of cancer, but resistance is common. Recent findings indicate that antiviral type I interferon (IFN) signaling is induced by these treatments. However, the underlying mechanisms still need to be elucidated. Expression of a set of IFN-stimulated genes comprises an IFN-related DNA damage resistance signature (IRDS), which correlates strongly with resistance to radiotherapy and chemotherapy across different tumors. Classically, during viral infection, the presence of foreign DNA in the cytoplasm of host cells can initiate type I IFN signaling...
March 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28279792/transcriptome-data-analysis-of-grass-carp-ctenopharyngodon-idella-infected-by-reovirus-provides-insights-into-two-immune-related-genes
#17
Zao Dai, Jicheng Li, Chengyu Hu, Fang Wang, Binhua Wang, Xiao Shi, Qunhao Hou, Waigen Huang, Gang Lin
Grass carp (Ctenopharyngodon idella) was one of the economically important freshwater fish in China. However, hemorrhagic disease caused by grass carp reovirus (GCRV) results in a tremendous loss in the process of grass carp cultivation. Transcriptome analysis could provide a comprehensive understanding of the molecular mechanisms involved in specific biological processes and diseases for the resistance to reovirus infection of grass carp. In this study, the raw data from NCBI (accession number: SRA099702) were analyzed, in which, 50 significant differentially expressed genes by routine transcriptome analysis and 84 notably differentially expressed genes by co-expression network method...
March 6, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28279190/imiquimod-has-strain-dependent-effects-in-mice-and-does-not-uniquely-model-human-psoriasis
#18
William R Swindell, Kellie A Michaels, Andrew J Sutter, Doina Diaconu, Yi Fritz, Xianying Xing, Mrinal K Sarkar, Yun Liang, Alex Tsoi, Johann E Gudjonsson, Nicole L Ward
BACKGROUND: Imiquimod (IMQ) produces a cutaneous phenotype in mice frequently studied as an acute model of human psoriasis. Whether this phenotype depends on strain or sex has never been systematically investigated on a large scale. Such effects, however, could lead to conflicts among studies, while further impacting study outcomes and efforts to translate research findings. METHODS: RNA-seq was used to evaluate the psoriasiform phenotype elicited by 6 days of Aldara (5% IMQ) treatment in both sexes of seven mouse strains (C57BL/6 J (B6), BALB/cJ, CD1, DBA/1 J, FVB/NJ, 129X1/SvJ, and MOLF/EiJ)...
March 9, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28276468/nv-proteins-of-fish-novirhabdovirus-recruit-cellular-ppm1bb-protein-phosphatase-and-antagonize-rig-i-mediated-ifn-induction
#19
Stéphane Biacchesi, Emilie Mérour, Didier Chevret, Annie Lamoureux, Julie Bernard, Michel Brémont
Non virion (NV) protein expression is critical for fish Novirhabdovirus, viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV), in vivo pathogenesis. However, the mechanism by which NV promotes the viral replication is still unclear. We developed an approach based on reverse genetics and interactomic and identified several NV-associated cellular partners underlying cellular pathways as potential viral targets. Among these cell partners, we showed that NV proteins specifically interact with a protein phosphatase, Mg(2+)/Mn(2+)-dependent, 1Bb (PPM1Bb) and recruit it in the close vicinity of mitochondria, a subcellular compartment important for retinoic acid-inducible gene-I- (RIG-I)-mediated interferon induction pathway...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274837/a-novel-method-for-detection-of-ifn-lambda-3-binding-to-cells-for-quantifying-ifn-lambda-receptor-expression
#20
Deanna M Santer, Gillian E S Minty, Adil Mohamed, Lesley Baldwin, Rakesh Bhat, Michael Joyce, Adrian Egli, D Lorne J Tyrrell, Michael Houghton
Type III interferons (IFN-lambdas) are important antiviral cytokines that also modulate immune responses acting through a unique IFN-λR1/IL-10R2 heterodimeric receptor. Conflicting data has been reported for which cells express the IFN-λR1 subunit and directly respond to IFN-λs. In this study we developed a novel method to measure IFN-λ3 binding to IFN-λR1/IL-10R2 on the surface of cells and relate this to a functional readout of interferon stimulated gene (ISG) activity in various cell lines. We show that Huh7...
March 5, 2017: Journal of Immunological Methods
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