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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/29348882/microrna203a-suppresses-glioma-tumorigenesis-through-an-atm-dependent-interferon-response-pathway
#1
Chuan He Yang, Yinan Wang, Michelle Sims, Chun Cai, Ping He, Hans Häcker, Junming Yue, Jinjun Cheng, Frederick A Boop, Lawrence M Pfeffer
Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM tumorigenesis in vivo...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348297/changes-in-macrophage-transcriptome-associate-with-systemic-sclerosis-and-mediate-gsdma-contribution-to-disease-risk
#2
Aida Moreno-Moral, Marta Bagnati, Surya Koturan, Jeong-Hun Ko, Carmen Fonseca, Nathan Harmston, Laurence Game, Javier Martin, Voon Ong, David J Abraham, Christopher P Denton, Jacques Behmoaras, Enrico Petretto
OBJECTIVES: Several common and rare risk variants have been reported for systemic sclerosis (SSc), but the effector cell(s) mediating the function of these genetic variants remains to be elucidated. While innate immune cells have been proposed as the critical targets to interfere with the disease process underlying SSc, no studies have comprehensively established their effector role. Here we investigated the contribution of monocyte-derived macrophages (MDMs) in mediating genetic susceptibility to SSc...
January 17, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29346611/combined-roles-of-atp-and-small-hairpin-rna-in-the-activation-of-rig-i-revealed-by-solution-based-analysis
#3
Neelam Shah, Simone A Beckham, Jacqueline A Wilce, Matthew C J Wilce
RIG-I (retinoic acid inducible gene-I) is a cytosolic innate immune protein that senses viral dsRNA with a 5'-triphosphate overhang. Upon interaction with dsRNA a de-repression of the RIG-I CARD domains takes place that ultimately leads to the production of type I interferons and pro-inflammatory cytokines. Here we investigate the RIG-I conformational rearrangement upon interaction with an activating 5'-triphosphate-10-base pair dsRNA hairpin loop (10bp) compared with a less active 5'-triphosphate-8-base pair dsRNA hairpin loop (8bp)...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29346345/the-cytosolic-sensor-sting-is-required-for-intestinal-homeostasis-and-control-of-inflammation
#4
M C C Canesso, L Lemos, T C Neves, F M Marim, T B R Castro, É S Veloso, C P Queiroz, J Ahn, H C Santiago, F S Martins, J Alves-Silva, E Ferreira, D C Cara, A T Vieira, G N Barber, S C Oliveira, A M C Faria
STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29345061/monocyte-subsets-exhibit-transcriptional-plasticity-and-a-shared-response-to-interferon-in-siv-infected-rhesus-macaques
#5
Brian T Nowlin, John Wang, Jamie L Schafer, Patrick Autissier, Tricia H Burdo, Kenneth C Williams
The progression to AIDS is influenced by changes in the biology of heterogeneous monocyte subsets. Classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes may represent progressive stages of monocyte maturation or disparate myeloid lineages with different turnover rates and function. To investigate the relationship between monocyte subsets and the response to SIV infection, we performed microarray analysis of monocyte subsets in rhesus macaques at three time points: prior to SIV infection, 26 days postinfection, and necropsy with AIDS...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29343571/casein-kinase-1%C3%AE-mediates-degradation-of-receptors-for-type-i-and-type-ii-interferons-caused-by-hemagglutinin-of-influenza-a-virus
#6
Chuan Xia, Jennifer J Wolf, Madhuvanthi Vijayan, Caleb J Studstill, Wenjun Ma, Bumsuk Hahm
Although influenza A virus (IAV) evades cellular defense systems to effectively propagate in the host, the viral immune evasive mechanisms are incompletely understood. Our recent data showed that hemagglutinin (HA) of IAV induces degradation of type I IFN receptor 1 (IFNAR1). Here, we demonstrate that IAV HA induces degradation of type II IFN (IFN-γ) receptor 1 (IFNGR1) as well as IFNAR1 via casein kinase 1α (CK1α), resulting in the impairment of cellular responsiveness to both type I and II IFNs. IAV infection or transient HA expression induced degradation of both IFNGR1 and IFNAR1, whereas HA gene-deficient IAV failed to downregulate the receptors...
January 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29342871/interferons-reprogramming-the-metabolic-network-against-viral-infection
#7
REVIEW
Kavita Raniga, Chen Liang
Viruses exploit the host and induce drastic metabolic changes to ensure an optimal environment for replication and the production of viral progenies. In response, the host has developed diverse countermeasures to sense and limit these alterations to combat viral infection. One such host mechanism is through interferon signaling. Interferons are cytokines that enhances the transcription of hundreds of interferon-stimulated genes (ISGs) whose products are key players in the innate immune response to viral infection...
January 13, 2018: Viruses
https://www.readbyqxmd.com/read/29342134/chromosomal-instability-drives-metastasis-through-a-cytosolic-dna-response
#8
Samuel F Bakhoum, Bryan Ngo, Ashley M Laughney, Julie-Ann Cavallo, Charles J Murphy, Peter Ly, Pragya Shah, Roshan K Sriram, Thomas B K Watkins, Neil K Taunk, Mercedes Duran, Chantal Pauli, Christine Shaw, Kalyani Chadalavada, Vinagolu K Rajasekhar, Giulio Genovese, Subramanian Venkatesan, Nicolai J Birkbak, Nicholas McGranahan, Mark Lundquist, Quincey LaPlant, John H Healey, Olivier Elemento, Christine H Chung, Nancy Y Lee, Marcin Imielenski, Gouri Nanjangud, Dana Pe'er, Don W Cleveland, Simon N Powell, Jan Lammerding, Charles Swanton, Lewis C Cantley
Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29338588/epstein-barr-virus-infection-and-type-i-interferon-signature-in-patients-with-systemic-lupus-erythematosus
#9
L Han, Y Zhang, Q Wang, M Xin, K Yang, K Lei, M Sun
Epstein-Barr (EB) virus infection has long been speculated to evoke systemic lupus erythematosus (SLE). Since a virus infection can induce interferon (IFN) system activation, we aimed to discover the relationship between the two in the progression of SLE in a Chinese inpatient cohort. Methods Peripheral blood mononuclear cells and sera were isolated from 116 SLE patients and 76 healthy controls. Antibodies against EBV-VCA (IgM and IgG) and EBNA (IgG) along with IFNα in patient sera were detected with enzyme-linked immunosorbent assays...
January 1, 2018: Lupus
https://www.readbyqxmd.com/read/29338543/lucidone-suppresses-dengue-viral-replication-through-the-induction-of-heme-oxygenase-1
#10
Wei-Chun Chen, Chin-Kai Tseng, Chun-Kuang Lin, Shen-Nien Wang, Wen-Hung Wang, Shih-Hsien Hsu, Yu-Hsuan Wu, Ling-Chien Hung, Yen-Hsu Chen, Jin-Ching Lee
Dengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice...
January 17, 2018: Virulence
https://www.readbyqxmd.com/read/29337425/distinct-gene-expression-profiles-and-regulation-networks-of-nasal-polyps-in-eosinophilic-and-non-eosinophilic-chronic-rhinosinusitis
#11
Naoko Okada, Tsuguhisa Nakayama, Daiya Asaka, Natsuki Inoue, Tadao Tsurumoto, Shinya Takaishi, Nobuyoshi Otori, Hiromi Kojima, Akio Matsuda, Keisuke Oboki, Hirohisa Saito, Kenji Matsumoto, Mamoru Yoshikawa
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is known to have 2 phenotypes in East Asia. Eosinophilic CRSwNP (ECRSwNP), defined as tissue eosinophilia and easily recurrent, is distinguished from other non-eosinophilic CRSwNP (NECRSwNP) types. However, the pathogenesis of each remains unclear. METHODS: Nasal polyp tissues from ECRS (ECRSwNP) and NECRS (NECRSwNP) patients were obtained, and their comprehensive gene expression profiles were investigated by microarray analysis...
January 16, 2018: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29333035/the-activity-of-immunoglobulin-y-anti-mycobacterium-tuberculosis-on-proliferation-and-cytokine-expression-of-rat-peripheral-blood-mononuclear-cells
#12
Sri Agus Sudjarwo, Koerniasari Eraiko, Giftania Wardani Sudjarwo, Koerniasari
Objective: It has long been known that chickens, like mammals, are capable of producing antigen-specific immunoglobulin Y (IgY), which functions similar to IgG. The present study was performed to investigate the activity of IgY anti-Mycobacterium tuberculosis on proliferation, interleukin (IL)-2, and interferon (IFN)-γ expression of rat peripheral blood mononuclear cells (PBMCs). Materials and Methods: The activity of IgY anti-M. tuberculosis in different doses (25, 50, and 100 μg/ml) on rat PBMCs proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29330447/human-placental-derived-adherent-stromal-cells-co-induced-with-tnf-%C3%AE-and-ifn-%C3%AE-inhibit-triple-negative-breast-cancer-in-nude-mouse-xenograft-models
#13
Hoshea Allen, Niva Shraga-Heled, Michal Blumenfeld, Tamar Dego-Ashto, Dana Fuchs-Telem, Ariel Gilert, Zami Aberman, Racheli Ofir
Culturing 3D-expanded human placental-derived adherent stromal cells (ASCs) in the presence of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) transiently upregulated the secretion of numerous anti-proliferative, anti-angiogenic and pro-inflammatory cytokines. In a 3D-spheroid screening assay, conditioned medium from these induced-ASCs inhibited proliferation of cancer cell lines, including triple-negative breast cancer (TNBC) lines. In vitro co-culture studies of induced-ASCs with MDA-MB-231 human breast carcinoma cells, a model representing TNBC, supports a mechanism involving immunomodulation and angiogenesis inhibition...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330299/effects-of-allelic-variations-in-the-human-myxovirus-resistance-protein-a-on-its-antiviral-activity
#14
Laura Graf, Alexej Dick, Franziska Sendker, Emanuel Barth, Manja Marz, Oliver Daumke, Georg Kochs
Only a minority of patients infected with seasonal influenza A viruses exhibits a severe or fatal outcome of infection, but the reasons for this inter-individual variability in influenza susceptibility are unclear. To gain further insights into the molecular mechanisms underlying this variability, we investigated naturally occurring allelic variations of the myxovirus resistance 1 (MX1) gene coding for the influenza restriction factor MxA. The interferon-induced dynamin-like GTPase consists of an N-terminal GTPase domain, a bundle signaling element, and a C-terminal stalk responsible for oligomerization and viral target recognition...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29324751/stage-specific-ifn-induced-and-ifn-gene-expression-reveal-convergence-of-type-i-and-type-ii-ifn-and-highlight-their-role-in-both-acute-and-chronic-stage-of-pathogenic-siv-infection
#15
Nadia Echebli, Nicolas Tchitchek, Stéphanie Dupuy, Timothée Bruel, Caroline Peireira Bittencourt Passaes, Nathalie Bosquet, Roger Le Grand, Christine Bourgeois, Benoit Favier, Rémi Cheynier, Olivier Lambotte, Bruno Vaslin
Interferons (IFNs) play a major role in controlling viral infections including HIV/SIV infections. Persistent up-regulation of interferon stimulated genes (ISGs) is associated with chronic immune activation and progression in SIV/HIV infections, but the respective contribution of different IFNs is unclear. We analyzed the expression of IFN genes and ISGs in tissues of SIV infected macaques to understand the respective roles of type I and type II IFNs. Both IFN types were induced in lymph nodes during early stage of primary infection and to some extent in rectal biopsies but not in PBMCs...
2018: PloS One
https://www.readbyqxmd.com/read/29324236/irf1-up-regulates-isg15-gene-expression-in-dsrna-stimulation-or-csfv-infection-by-targeting-nucleotides-487-to-325-in-the-5-flanking-region
#16
Xiao-Quan Li, Xiao Ning Li, Jing-Jing Liang, Xin-Bin Cai, Qian Tao, Yu-Xiao Li, Qing Qin, Su-Ping Xu, Ting Rong Luo
Interferon (IFN)-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is heavily involved in immune response elicitation. As an important member of interferon regulatory factor (IRF) family, IRF1 can activate the expression of multiple genes, including the human optineurin gene (Sudhakar et al., 2013). In this study, a sequence in the promoter region of the optineurin gene was compared to the 5' flanking region of the porcine isg15 gene. Porcine IRF1 also possesses antiviral activity against several swine viruses (Li et al...
January 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29321318/viperin-restricts-zika-virus-and-tick-borne-encephalitis-virus-replication-by-targeting-ns3-for-proteasomal-degradation
#17
Christakis Panayiotou, Richard Lindqvist, Chaitanya Kurhade, Kirstin Vonderstein, Jenny Pasto, Karin Edlund, Arunkumar S Upadhyay, Anna K Överby
Flaviviruses are arthropod-borne viruses that constitute a major global health problem, with millions of human infections annually. Their pathogenesis ranges from mild illness to severe manifestations such as hemorrhagic fever and fatal encephalitis. Type I interferons (IFNs) are induced in response to viral infection, and stimulate the expression of interferon-stimulated genes (ISGs), including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum-associated, IFN-inducible), which shows antiviral activity against a broad spectrum of viruses including several flaviviruses...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321042/type-i-ifn-signature-in-childhood-onset-systemic-lupus-erythematosus-a-conspiracy-of-dna-and-rna-sensing-receptors
#18
M Javad Wahadat, Iris L A Bodewes, Naomi I Maria, Cornelia G van Helden-Meeuwsen, Annette van Dijk-Hummelman, Eline C Steenwijk, Sylvia Kamphuis, Marjan A Versnel
BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is an incurable multi-systemic autoimmune disease. Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. The objective of this study was to assess the prevalence of the IFN-I signature and the contribution of cytosolic nucleic acid receptors to IFN-I activation in a cohort of primarily white cSLE patients. METHODS: The IFN-I score (positive or negative), as a measure of IFN-I activation, was assessed using real-time quantitative PCR (RT-PCR) expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)...
January 10, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29320737/genomic-circuitry-underlying-immunological-response-to-pediatric-acute-respiratory-infection
#19
Sarah E Henrickson, Sasikanth Manne, Douglas V Dolfi, Kathleen D Mansfield, Kaela Parkhouse, Rakesh D Mistry, Elizabeth R Alpern, Scott E Hensley, Kathleen E Sullivan, Susan E Coffin, E John Wherry
Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29320694/dynamic-structural-differences-between-human-and-mouse-sting-lead-to-differing-sensitivity-to-dmxaa
#20
Amy Y Shih, Kelly L Damm-Ganamet, Taraneh Mirzadegan
The stimulator-of-interferon-genes (STING) protein is involved in innate immunity. It has recently been shown that modulation of STING can lead to an aggressive antitumor response. DMXAA is an antitumor agent that had shown great promise in murine models but failed in human clinical trials. The molecular target of DMXAA was subsequently shown to be murine STING (mSTING); however, human STING (hSTING) is insensitive to DMXAA. Molecular dynamics simulations were employed to investigate the differences between hSTING and mSTING that could influence DMXAA binding...
January 9, 2018: Biophysical Journal
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