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Stimulator of interferon genes

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https://www.readbyqxmd.com/read/28642132/unphosphorylated-stat3-regulates-the-antiproliferative-antiviral-and-gene-inducing-actions-of-type-i-interferons
#1
Susan R Pfeffer, Meiyun Fan, Ziyun Du, Chuan He Yang, Lawrence M Pfeffer
Type I interferon (IFNα/β) induces antiviral and antiproliferative responses in cells through the induction of IFN-stimulated genes (ISGs). Although the roles of IFN-activated STAT1 and STAT2 in the IFN response are well described, the function of STAT3 is poorly characterized. We investigated the role of STAT3 in the biological response to IFNα/β in mouse embryonic fibroblasts (MEFs) with a germ line deletion of STAT3. These STAT3 knockout (STAT3-KO) MEFs were reconstituted with STAT3 or the F705-STAT3 mutant (unphosphorylated STAT3) where the canonical Y705 tyrosine phosphorylation site was mutated...
June 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28639887/microrna-138-enhances-trail-induced-apoptosis-through-interferon-stimulated-gene-15-downregulation-in-hepatocellular-carcinoma-cells
#2
Chaohui Zuo, Xinyi Sheng, Zhuo Liu, Min Ma, Shuhan Xiong, Hongyu Deng, Sha Li, Darong Yang, Xiaohong Wang, Hua Xiao, Hu Quan, Man Xia
Hepatocellular carcinoma is a leading cause of cancer-related mortality worldwide. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potential target for cancer therapy. However, many cancer cells are resistant to TRAIL-induced apoptosis and its mechanism is not well understood. In this study, to identify potential therapeutic targets for TRAIL-resistant cancer cells, we compared the expression levels of interferon-stimulated gene 15 in TRAIL-sensitive and TRAIL-resistant hepatocellular carcinoma cell lines...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639100/sting-mediated-dna-sensing-in-cancer-immunotherapy
#3
REVIEW
Xiang Zhou, Zhengfan Jiang
While STING (STimulator of INterferon Genes) has been shown to be essential for cytosolic DNA-triggered innate immune activation, accumulated evidence obtained from various studies suggested that an intrinsic relevance of STING-associated signaling in tumorigenesis can be observed. Also, several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for STING, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents...
May 29, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28637751/ifit2-is-a-restriction-factor-in-rabies-virus-pathogenicity
#4
Benjamin M Davis, Volker Fensterl, Tessa M Lawrence, Andrew W Hudacek, Ganes C Sen, Matthias J Schnell
Understanding the interactions between rabies virus (RABV) and individual host cell proteins is critical for the development of targeted therapies. Here we report that Interferon-induced protein with tetratricopeptide repeats 2 (Ifit2), an interferon-stimulated gene (ISG) with possible RNA-binding capacity, is an important restriction factor for rabies virus. When Ifit2 was depleted, RABV grew more quickly in mouse neuroblastoma in vitro This effect was replicated in vivo, where Ifit2 knockout mice displayed a dramatically more severe disease phenotype than wild-type after intranasal inoculation of RABV...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28634115/delineating-the-roles-of-cellular-and-innate-antiviral-immune-parameters-mediating-ranavirus-susceptibility-using-rainbow-trout-cell-lines
#5
Graeme J Lisser, Nguyen T K Vo, Stephanie J DeWitte-Orr
Frog virus 3 is the type species of the Ranavirus genus and the causative agent of massive mortalities of aquatic species worldwide. A critical step in limiting virus replication, particularly early in infection, is the innate immune response. Presently, little is known regarding what innate immune strategies limit FV3 at the cellular level. To this end, the present study uses two rainbow trout cell lines, RTG-2 and RTgutGC, which demonstrate susceptible and relatively resistant phenotypes to FV3 infection, to elucidate susceptibility factors to FV3...
June 17, 2017: Virus Research
https://www.readbyqxmd.com/read/28631605/loss-of-sendai-virus-c-protein-leads-to-accumulation-of-rig-i-immunostimulatory-defective-interfering-rna
#6
Maria Teresa Sánchez-Aparicio, Dominique Garcin, Charles M Rice, Daniel Kolakofsky, Adolfo García-Sastre, Alina Baum
Retinoic acid inducible gene (RIG-I)-mediated innate immunity plays a pivotal role in defence against virus infections. Previously we have shown that Sendai virus (SeV) defective interfering (DI) RNA functions as an exclusive and potent RIG-I ligand in DI-RNA-rich SeV-Cantell infected cells. To further understand how RIG-I is activated during SeV infection, we used a different interferon (IFN)-inducing SeV strain, recombinant SeVΔC, which, in contrast to SeV-Cantell is believed to stimulate IFN production due to the lack of the SeV IFN antagonist protein C...
June 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28626076/cardiac-fibroblast-transcriptome-analyses-support-a-role-for-interferogenic-profibrotic-and-inflammatory-genes-in-anti-ssa-ro-associated-congenital-heart-block
#7
Robert M Clancy, Androo J Markham, Tanisha Jackson, Sara E Rasmussen, Miroslav Blumenberg, Jill P Buyon
The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated hY3. The top ten upregulated transcripts in the stimulated fibroblasts reflected a type I interferon (IFN) response (e...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28625530/the-emerging-roles-of-sting-in-bacterial-infections
#8
REVIEW
Fabio V Marinho, Sulayman Benmerzoug, Sergio C Oliveira, Bernhard Ryffel, V F J Quesniaux
The STING (Stimulator of Interferon Genes) protein connects microorganism cytosolic sensing with effector functions of the host cell by sensing directly cyclic dinucleotides (CDNs), originating from pathogens or from the host upon DNA recognition. Although STING activation favors effective immune responses against viral infections, its role during bacterial diseases is controversial, ranging from protective to detrimental effects for the host. In this review, we summarize important features of the STING activation pathway and recent highlights about the role of STING in bacterial infections by Chlamydia, Listeria, Francisella, Brucella, Shigella, Salmonella, Streptococcus, and Neisseria genera, with a special focus on mycobacteria...
June 15, 2017: Trends in Microbiology
https://www.readbyqxmd.com/read/28623559/ifn-%C3%AE-induced-reactive-oxygen-species-and-mitochondrial-damage-contribute-to-muscle-impairment-and-inflammation-maintenance-in-dermatomyositis
#9
Alain Meyer, Gilles Laverny, Yves Allenbach, Elise Grelet, Vanessa Ueberschlag, Andoni Echaniz-Laguna, Béatrice Lannes, Ghada Alsaleh, Anne Laure Charles, François Singh, Joffrey Zoll, Evelyne Lonsdorfer, François Maurier, Olivier Boyer, Jacques-Eric Gottenberg, Anne Sophie Nicot, Jocelyn Laporte, Olivier Benveniste, Daniel Metzger, Jean Sibilia, Bernard Geny
Dermatomyositis (DM) is an autoimmune disease associated with enhanced type I interferon (IFN) signalling in skeletal muscle, but the mechanisms underlying muscle dysfunction and inflammation perpetuation remain unknown. Transcriptomic analysis of early untreated DM muscles revealed that the main cluster of down-regulated genes was mitochondria-related. Histochemical, electron microscopy, and in situ oxygraphy analysis showed mitochondrial abnormalities, including increased reactive oxygen species (ROS) production and decreased respiration, which was correlated with low exercise capacities and a type I IFN signature...
June 16, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28622863/down-regulating-heat-shock-protein-27-is-involved-in-porcine-epidemic-diarrhea-virus-escaping-from-host-antiviral-mechanism
#10
Min Sun, Zeyanqiu Yu, Jiale Ma, Zihao Pan, Chengping Lu, Huochun Yao
Porcine epidemic diarrhea virus (PEDV), is the etiological agent of porcine epidemic diarrhea virus (PED), causes high mortality with severe vomiting, diarrhea, and dehydration in swine farms. In this study, the PEDV strain 85-7 could be proliferated effectively in MARC-145 cells, and caused a distinct inhibition of the expression of interferon-β (IFN-β, encoded by IFNB1), which suggested that a full understanding how this virus manipulates the host immune responses is critical in the fight against the spread of PEDV...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28622443/mir-2909-regulates-isgylation-system-via-stat1-signalling-through-negative-regulation-of-socs3-in-prostate-cancer
#11
Shiekh Gazalla Ayub, Deepak Kaul
One of the well-document strategies adopted by tumour cells for progression is to evade immune surveillance mechanisms. An understanding of the tight interaction between immunity and progression of cancer can provide novel treatment options for different malignancies including prostate cancer (PCa). Here, we have shown that AATF genome encoded miR-2909, known to play role both in immunity and cancer upregulates various interferon stimulating genes (ISGs) including ISGylation system through STAT1. Our results revealed that miR-2909 up-regulates STAT1 through negative regulation of SOCS3 and not through up-regulation of Type 1 interferon (IFN) production...
June 16, 2017: Andrology
https://www.readbyqxmd.com/read/28620129/up-regulation-of-irf-3-expression-through-gata-1-acetylation-by-histone-deacetylase-inhibitor-in-lung-adenocarcinoma-a549-cells
#12
Lu-Lu Wang, Lan-Bo Zhou, Jin Shu, Nan-Nan Li, Hui-Wen Zhang, Rui Jin, Li-Li Zhuang, Guo-Ping Zhou
Interferon regulatory factor 3 (IRF-3) is an important transcription factor for interferon genes. Although its functional activation by viral infection has been widely explicated, the regulatory mechanism of IRF-3 gene expression in cancer cells is poorly understood. In this study, we demonstrated treatment of lung adenocarcinoma A549 cells with trichostatin A (TSA) and valproic acid (VPA), two different classes of histone deacetylase inhibitors, strongly stimulated IRF-3 gene expression. Truncated and mutated IRF-3 promoter indicated that a specific GATA-1 element was responsible for TSA-induced activation of IRF-3 promoter...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619150/alpha-beta-interferon-receptor-deficiency-in-mice-significantly-enhances-susceptibility-of-the-animals-to-pseudorabies-virus-infection
#13
Jingyun Wei, Yanmei Ma, Long Wang, Xiaojuan Chi, Ruoxiang Yan, Song Wang, Xinxin Li, Xiaoyong Chen, Wenhan Shao, Ji-Long Chen
Pseudorabies virus, one of the neurotropic viruses, can infect numerous mammals. In particular, pseudorabies virus infection of swine occurs worldwide, and is a major threat to swine industry. However, the mechanism underlying the interaction between pseudorabies virus and host innate immune system is not fully understood. Here, we investigated the involvement of interferon α/β (IFN-α/β) receptor (IFNAR) in the pathogenesis of pseudorabies virus in a mouse model. The results showed that IFNAR-deficient (IFNAR(-/-)) mice were highly susceptible to the virus infection, as evidenced by markedly reduced survival rate of infected animals and increased viral replication...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28615418/cutting-edge-activation-of-sting-in-t-cells-induces-type-i-ifn-responses-and-cell-death
#14
Bridget Larkin, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Edouard Vannier, Alexander Poltorak
Stimulator of interferon genes (STING) was initially described as a sensor of intracellular bacterial and viral DNA and a promising adjuvant target in innate immune cells; more recently STING has also been shown to detect endogenous DNA and play a role in tumor immunity and autoimmune disease development. Thus far STING has been studied in macrophages and dendritic cells. In this study, to our knowledge we provide the first evidence of STING activation in T cells, in which STING agonists not only provoke type I IFN production and IFN-stimulated gene expression, mirroring the response of innate cells, but are also capable of activating cell stress and death pathways...
June 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28614370/the-hemagglutinin-neuramidinase-protein-of-newcastle-disease-virus-upregulates-expression-of-the-trail-gene-in-murine-natural-killer-cells-through-the-activation-of-syk-and-nf-%C3%AE%C2%BAb
#15
Ying Liang, De-Zhi Song, Shuang Liang, Zeng-Feng Zhang, Ling-Xi Gao, Xiao-Hui Fan
Newcastle disease virus (NDV) is responsible for tumoricidal activity in vitro and in vivo. However, the mechanisms that lead to this activity are unclear. Natural killer cells are able to induce apoptosis of tumor cells through multiple pathways, including the tumor necrosis factor-related apoptosis-inducing ligand-death receptor pathway. We previously showed that exposure of NK and T cells to NDV resulted in enhanced tumoricidal activity that was mediated by upregulated expression of the TRAIL gene, via an interferon gamma -dependent pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28605413/acute-bovine-viral-diarrhoea-virus-infection-inhibits-expression-of-interferon-tau-stimulated-genes-in-bovine-endometrium
#16
Zhangrui Cheng, Latta Chauhan, Amy Teresa Barry, Ayimuguli Abudureyimu, Chike F Oguejiofor, Xing Chen, D Claire Wathes
Bovine viral diarrhoea virus (BVDV) can evade host detection by down-regulation of interferon signalling pathways. Infection of cows with non-cytopathic (ncp) BVDV can cause early embryonic mortality. Upregulation of type I interferon stimulated genes (ISGs) by blastocyst-secreted interferon tau (IFNT) is a crucial component of the maternal recognition of pregnancy (MRP) in ruminants. This study investigated the potential of acute BVDV infection to disrupt MRP by modulating endometrial ISG expression. Endometrial cells from 10 BVDV-free cows were cultured and treated with 0 or 100 ng/ml IFNT for 24 h in the absence or presence of ncpBVDV infection to yield 4 treatment groups: CONT, ncpBVDV, IFNT or ncpBVDV+IFNT...
June 12, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28605144/musculoskeletal-disease-in-mda5-related-type-i-interferonopathy-a-mendelian-mimic-of-jaccoud-s-arthropathy
#17
Luciana Martins de Carvalho, Gonza Ngoumou, Ji Woo Park, Nadja Ehmke, Nikolaus Deigendesch, Naoki Kitabayashi, Isabelle Melki, Flávio Falcäo L Souza, Andreas Tzschach, Marcello H Nogueira-Barbosa, Virgínia Ferriani, Paulo Louzada-Junior, Wilson Marques Junior, Charles M Lourenço, Prof Denise Horn, Tilmann Kallinich, Werner Stenzel, Sun Hur, Gillian I Rice, Yanick J Crow
Objectives To define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet including camptodactyly, subluxation and tendon rupture reminiscent of Jaccoud's arthropathy. Methods We ascertained two families segregating an autosomal dominant phenotype encompassing musculoskeletal disease and variable additional features including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma and basal ganglia calcification. We measured the expression of interferon-stimulated genes in peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA sensor MDA5...
June 12, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28602976/sting-signaling-in-tumorigenesis-and-cancer-therapy-a-friend-or-foe
#18
Liangmei He, Xiaomei Xiao, Xi Yang, Zixiang Zhang, Wu Longhuo, Zhiping Liu
Stimulator of interferon genes (STING) is a DNA sensor and an important cytoplasmic adaptor for other DNA sensors, such as Z-DNA binding protein 1 (DAI), DEAD-box helicase 41 (DDX41), and interferon-γ-inducible protein 16 (IFI16). The activation of STING signaling leads to the production of type I interferons and some other pro-inflammatory cytokines, and is critical for host defense against viral infection. Recent accumulating evidences suggest that STING is also involved in tumor development. However, the role of STING signaling in tumorigenesis is complicated, and a comprehensive review is still lacking...
June 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28602862/sag5b-and-sag5c-combined-vaccine-protects-mice-against-toxoplasma-gondii-infection
#19
Gang Lu, Jian Zhou, Aihua Zhou, Yali Han, Jingjing Guo, Pengxia Song, Huaiyu Zhou, Hua Cong, Ming Hou, Lin Wang, Shenyi He
Infections with the protozoan parasite Toxoplasma gondii, which are common around the world, can lead to congenital infections in humans. T. gondii surface antigen protein 5B (SAG5B) and SAG5C are potential stimulators of humoral and cellular immune responses. In this study, a multi-antigenic DNA vaccine constructed to express T. gondii SAG5B and SAG5C proteins simultaneously was used to immunize BALB/c mice to evaluate the protective efficacy of the vaccine. IgG antibody and gamma interferon (IFN-γ) cytokine production in the pSAG5B/SAG5C DNA vaccine group were significantly higher (0...
June 8, 2017: Parasitology International
https://www.readbyqxmd.com/read/28601944/glucocorticoid-induced-leucine-zipper-expression-is-associated-with-response-to-treatment-and-immunoregulation-in-systemic-lupus-erythematosus
#20
Saeed Mohammadi, Mohammad Reza Ebadpour, Sima Sedighi, Mohsen Saeedi, Ali Memarian
Systemic lupus erythematosus (SLE) is an autoimmune disorder in which cytokine balance is disturbed. Glucocorticoids (GCs) are shown to balance immune response by transcriptional regulation of glucocorticoid receptor target genes such as Glucocorticoid-induced leucine zipper (GILZ) which has been introduced as an endogenous anti-inflammatory mediator. In the present study, we assessed the expression of GILZ in association with interferon-γ (IFN-γ), interleukine-10 (IL-10), and B lymphocyte stimulator (BLyS) plasma levels in SLE patients...
June 10, 2017: Clinical Rheumatology
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