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https://www.readbyqxmd.com/read/28500614/irf9-stat2-fusion-protein-as-an-innate-immune-inducer-to-activate-mx-and-interferon-stimulated-gene-expression-in-zebrafish-larvae
#1
Chang-Jen Huang, Chih-Ming Chou, Huang-Wei Lien, Cheng-Ying Chu, Jhih-Yun Ho, Yimin Wu, Chia-Hsiung Cheng
Virus infection often causes large amounts of mortality during teleost larvae stage. Strong induction of innate immunity to increase survival rates of teleost larvae has been less reported. In this study, we present a zebrafish IRF9-Stat2 fusion protein (zIRF9-S2C) as a strong innate immunity inducer and characterized induction of interferon-stimulated genes (ISGs) in zebrafish larvae. zIRF9-S2C could mimic IFN-stimulated gene factor 3 (ISGF3) complex to constitutively activate transcription of Mx promoter through IFN-stimulatory element (ISRE) sites...
May 12, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28499943/molecular-cloning-transcriptional-profiling-and-subcellular-localization-of-signal-transducer-and-activator-of-transcription-2-stat2-ortholog-from-rock-bream-oplegnathus-fasciatus
#2
S D N K Bathige, Navaneethaiyer Umasuthan, Thanthrige Thiunuwan Priyathilaka, William Shanthakumar Thulasitha, J D H E Jayasinghe, Qiang Wan, Bo-Hye Nam, Jehee Lee
Signal transducer and activator of transcription 2 (STAT2) is a key element that transduces signals from the cell membrane to the nucleus via the type I interferon-signaling pathway. Although the structural and functional aspects of STAT proteins are well studied in mammals, information on teleostean STATs is very limited. In this study, a STAT paralog, which is highly homologous to the STAT2 members, was identified from a commercially important fish species called rock bream and designated as RbSTAT2. The RbSTAT2 gene was characterized at complementary DNA (cDNA) and genomic sequence levels, and was found to possess structural features common with its mammalian counterparts...
May 9, 2017: Gene
https://www.readbyqxmd.com/read/28494868/interferon-receptor-signaling-pathways-regulating-pd-l1-and-pd-l2-expression
#3
Angel Garcia-Diaz, Daniel Sanghoon Shin, Blanca Homet Moreno, Justin Saco, Helena Escuin-Ordinas, Gabriel Abril Rodriguez, Jesse M Zaretsky, Lu Sun, Willy Hugo, Xiaoyan Wang, Giulia Parisi, Cristina Puig Saus, Davis Y Torrejon, Thomas G Graeber, Begonya Comin-Anduix, Siwen Hu-Lieskovan, Robert Damoiseaux, Roger S Lo, Antoni Ribas
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28472186/stat2-is-involved-in-the-pathogenesis-of-psoriasis-by-promoting-cxcl11-and-ccl5-production-by-keratinocytes
#4
Claus Johansen, Anne Hald Rittig, Maike Mose, Trine Bertelsen, Isabella Weimar, Jakob Nielsen, Thomas Andersen, Tue Kruse Rasmussen, Bent Deleuran, Lars Iversen
The JAK/STAT signaling pathway is suggested to play an important role in the pathogenesis of psoriasis, and recently JAK/STAT inhibitors have shown promising results in psoriasis treatment. The present study aimed to characterize the role of STAT2 in psoriasis. We demonstrated an increased expression of STAT2 and an increased level of phosphorylated/activated STAT2 in lesional compared with nonlesional psoriatic skin. Gene silencing of STAT2 by siRNA in human keratinocytes revealed that upon IFNα stimulation CXCL11 and CCL5 were the only two cytokines, among 102 analyzed, found to be regulated through a STAT2-dependent mechanism...
2017: PloS One
https://www.readbyqxmd.com/read/28468880/selective-activation-of-interferon-%C3%AE-signaling-by-zika-virus-ns5-protein
#5
Vidyanath Chaudhary, Kit-San Yuen, Jasper Fuk-Woo Chan, Ching-Ping Chan, Pei-Hui Wang, Jian-Piao Cai, Shuo Zhang, Mifang Liang, Kin-Hang Kok, Chi-Ping Chan, Kwok-Yung Yuen, Dong-Yan Jin
Severe complications of Zika virus (ZIKV) infection might be caused by inflammation. How ZIKV induces pro-inflammatory cytokines is not understood. In this study, we show opposite regulatory effect of ZIKV NS5 protein on interferon (IFN) signaling. Whereas ZIKV and its NS5 protein were potent suppressors of type I and type III IFN signaling, they were found to activate IFN-γ signaling. Inversely, IFN-γ augmented ZIKV replication. NS5 interacted with STAT2 and targeted it for ubiquitination and degradation, but had no influence on STAT1 stability or nuclear translocation...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28442624/unphosphorylated-isgf3-drives-constitutive-expression-of-interferon-stimulated-genes-to-protect-against-viral-infections
#6
Wenshi Wang, Yuebang Yin, Lei Xu, Junhong Su, Fen Huang, Yijin Wang, Patrick P C Boor, Kan Chen, Wenhui Wang, Wanlu Cao, Xinying Zhou, Pengyu Liu, Luc J W van der Laan, Jaap Kwekkeboom, Maikel P Peppelenbosch, Qiuwei Pan
Interferon (IFN)-stimulated genes (ISGs) are antiviral effectors that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we found that IFN-independent ISG expression was detectable in immortalized cell lines, primary intestinal and liver organoids, and liver tissues. The constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U-ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and STAT2...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28441586/kobuvirus-vp3-protein-restricts-the-ifn-%C3%AE-triggered-signaling-pathway-by-inhibiting-stat2-irf9-and-stat2-stat2-complex-formation
#7
Qianqian Peng, Xi Lan, Chen Wang, Yujie Ren, Ningning Yue, Junyong Wang, Bo Zhong, Qiyun Zhu
Emerged porcine kobuvirus (PKV) has adversely affected the global swine industry since 2008, but the etiological biology of PKV is unclear. Screening PKV-encoded structural and non-structural proteins with a type I IFN-responsive luciferase reporter showed that PKV VP3 protein inhibited the IFN-β-triggered signaling pathway, resulting in the decrease of VSV-GFP replication. QPCR data showed that IFN-β downstream cytokine genes were suppressed without cell-type specificity as well. The results from biochemical experiments indicated that PKV VP3 associated with STAT2 and IRF9, and interfered with the formation of the STAT2-IRF9 and STAT2-STAT2 complex, impairing nuclear translocation of STAT2 and IRF9...
April 22, 2017: Virology
https://www.readbyqxmd.com/read/28440504/adipor1-mediated-mir-3908-inhibits-glioblastoma-tumorigenicity-through-downregulation-of-stat2-associated-with-the-ampk-sirt1-pathway
#8
Xiangming Liu, Jinglong Chen, Jinqian Zhang
A prospective method of treatment for cancer is to inhibit oncogene signaling pathways with microRNA (miRNA or miR). In the present study, whether the expression of STAT2, AdipoR1/AMPK/SIRT1 pathway of glioma is regulated by miR-3908 was explored. To confirm whether the predicted miR-3908 is matched with STAT2 and AdipoR1, 3'UTR luciferase activity of STAT2 and AdipoR1 was assessed. In the presence of the mimics or inhibitors of miR-3908, cell function of glioma cells, such as proliferation, growth, migration, invasion and apoptosis were analyzed...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28432122/dual-regulation-of-stat1-and-stat3-by-the-tumor-suppressor-protein-pml-contributes-to-ifn%C3%AE-mediated-inhibition-of-angiogenesis
#9
Kuo-Sheng Hsu, Xuan Zhao, Xiwen Cheng, Dongyin Guan, Ganapati H Mahabeleshwar, Yu Liu, Ernest Borden, Mukesh K Jain, Hung-Ying Kao
IFNs are effective in inhibiting angiogenesis in preclinical models and in treating several angio-proliferative disorders. However, the detailed mechanisms of IFNα-mediated anti-angiogenesis are not completely understood. Stat1/2/3 and PML are IFNα downstream effectors and are pivotal regulators of angiogenesis. Here, we investigated PML's role in the regulation of Stat1/2/3 activity. In Pml knockout (KO) mice, ablation of Pml largely reduces IFNα angiostatic ability in Matrixgel plug assays. This suggested an essential role for PML in IFNα's anti-angiogenic function...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431283/zika-virus-infection-of-adult-and-fetal-stat2-knock-out-hamsters
#10
Venkatraman Siddharthan, Arnaud J Van Wettere, Rong Li, Jinxin Miao, Zhongde Wang, John D Morrey, Justin G Julander
Zika virus (ZIKV) infection was investigated in adult and fetal STAT2 knock-out (KO) hamsters. Subcutaneous injection of ZIKV of adults resulted in morbidity, mortality, and infection of the uterus, placenta, brain, spinal cord, and testicles, thus providing an opportunity to evaluate congenital ZIKV infection in a second rodent species besides mice. ZIKV-infected cells with morphologies of Sertoli cells and spermatogonia were observed in the testes, which may have implications for sexual transmission and male sterility...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28427244/whole-genome-expression-analyses-of-type-2-diabetes-in-human-skin-reveal-altered-immune-function-and-burden-of-infection
#11
Chun Wu, Xiaopan Chen, Jing Shu, Chun-Ting Lee
Skin disorders are among most common complications associated with type 2 diabetes mellitus (T2DM). Although T2DM patients are known to have increased risk of infections and other T2DM-related skin disorders, their molecular mechanisms are largely unknown. This study aims to identify dysregulated genes and gene networks that are associated with T2DM in human skin. We compared the expression profiles of 56,318 transcribed genes on 74 T2DM cases and 148 gender- age-, and race-matched non-diabetes controls from the Genotype-Tissue Expression (GTEx) database...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422733/the-transcriptional-stat3-is-a-potential-target-whereas-transcriptional-stat5a-5b-6-are-new-biomarkers-for-prognosis-in-human-breast-carcinoma
#12
Hua-Tao Wu, Jing Liu, Guan-Wu Li, Jia-Xin Shen, Yi-Teng Huang
Signal Transducer and Activators of Transcription (STAT) is a set of transcription factors, involved in diverse cellular functions. Evidences from cell lines, mouse models and human tissues implicate these transcription factors in the oncogenesis of breast cancer. However, the diverse expression patterns and prognostic values of 7 STATs remain to be elucidated. In the current study, we mined the transcriptional and survival data of STATs in patients with breast carcinoma (BC) through ONCOMINE, bc-GenExMiner, Kaplan-Meier Plotter and cBioPortal...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28365387/structural-analysis-and-insight-into-zika-virus-ns5-mediated-interferon-inhibition
#13
Hamza Arshad Dar, Tahreem Zaheer, Rehan Zafar Paracha, Amjad Ali
The Zika virus outbreak in 2015-2016 is the largest of its kind for which WHO declared a Public Health Emergency of International Concerns. No FDA approved drug is available for the treatment of the viral infection. The interaction of flavivirus NS5 protein with SIAH2 ubiquitin ligase has been previously known. NS5 of Zika virus has been implicated in the degradation of STAT2 protein, which activates interferon-stimulated antiviral activity. Based on our proposition that NS5 utilizes SIAH2-mediated proteasomal degradation of STAT2, an in-silico study was carried out to characterize the protein-protein interactions between NS5, SIAH2 and STAT2 proteins...
March 30, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28347954/interaction-of-irf9-and-stat2-synergistically-up-regulates-ifn-and-pkr-transcription-in-ctenopharyngodon-idella
#14
REVIEW
Zhen Wu, Liqiang Wang, Xiaowen Xu, Gang Lin, Huiling Mao, Xiaoqin Ran, Tao Zhang, Keyi Huang, Haizhou Wang, Qingli Huang, Qun Xu, Chengyu Hu
IRF9 is a key factor in the JAK-STAT pathway. Under the stimulation of type I IFN, IRF9 interacts with STAT1 and STAT2 to form the IFN-I-stimulated gene factor 3 (ISGF3) which activates the transcription of ISG. However, many studies also showed that the dimmer IRF9/STAT2 rather than the tripolymer IRF9/STAT1/STAT2 acts as the ISGF3 in cells in response to IFN signals. In the present study, the full-length cDNA sequence of IRF9 (termed CiIRF9, KT601055) and STAT2 (term CiSTAT2, KT781914) from grass carp were cloned and identified...
March 24, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28319593/profiles-of-long-noncoding-rnas-in-hypertensive-rats-long-noncoding-rna-xr007793-regulates-cyclic-strain-induced-proliferation-and-migration-of-vascular-smooth-muscle-cells
#15
Qing-Ping Yao, Zhi-Wei Xie, Kai-Xuan Wang, Ping Zhang, Yue Han, Ying-Xin Qi, Zong-Lai Jiang
BACKGROUND: Long noncoding RNAs (lncRNAs) are being discovered in multiple diseases at a rapid pace. However, the contribution of lncRNAs to hypertension remains largely unknown. In hypertension, the vascular walls are exposed to abnormal mechanical cyclic strain, which leads to vascular remodelling. Here, we investigated the mechanobiological role of lncRNAs in hypertension. METHODS AND RESULTS: Differences in the lncRNAs and mRNAs between spontaneously hypertensive rats and Wistar-Kyoto rats were screened using a gene microarray...
June 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28295457/hepatic-ifit3-predicts-interferon-%C3%AE-therapeutic-response-in-patients-of-hepatocellular-carcinoma
#16
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/28288457/interferon-dependent-induction-of-clr-b-during-mouse-cytomegalovirus-infection-protects-bystander-cells-from-natural-killer-cells-via-nkr-p1b-mediated-inhibition
#17
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/28278235/a-novel-zika-virus-mouse-model-reveals-strain-specific-differences-in-virus-pathogenesis-and-host-inflammatory-immune-responses
#18
Shashank Tripathi, Vinod R M T Balasubramaniam, Julia A Brown, Ignacio Mena, Alesha Grant, Susana V Bardina, Kevin Maringer, Megan C Schwarz, Ana M Maestre, Marion Sourisseau, Randy A Albrecht, Florian Krammer, Matthew J Evans, Ana Fernandez-Sesma, Jean K Lim, Adolfo García-Sastre
Zika virus (ZIKV) is a mosquito borne flavivirus, which was a neglected tropical pathogen until it emerged and spread across the Pacific Area and the Americas, causing large human outbreaks associated with fetal abnormalities and neurological disease in adults. The factors that contributed to the emergence, spread and change in pathogenesis of ZIKV are not understood. We previously reported that ZIKV evades cellular antiviral responses by targeting STAT2 for degradation in human cells. In this study, we demonstrate that Stat2-/- mice are highly susceptible to ZIKV infection, recapitulate virus spread to the central nervous system (CNS), gonads and other visceral organs, and display neurological symptoms...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28276456/principal-components-analysis-based-unsupervised-feature-extraction-applied-to-gene-expression-analysis-of-blood-from-dengue-haemorrhagic-fever-patients
#19
Y-H Taguchi
Dengue haemorrhagic fever (DHF) sometimes occurs after recovery from the disease caused by Dengue virus (DENV), and is often fatal. However, the mechanism of DHF has not been determined, possibly because no suitable methodologies are available to analyse this disease. Therefore, more innovative methods are required to analyse the gene expression profiles of DENV-infected patients. Principal components analysis (PCA)-based unsupervised feature extraction (FE) was applied to the gene expression profiles of DENV-infected patients, and an integrated analysis of two independent data sets identified 46 genes as critical for DHF progression...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265273/new-data-on-human-macrophages-polarization-by-hymenolepis-diminuta-tapeworm-an-in-vitro-study
#20
Anna Zawistowska-Deniziak, Katarzyna Basałaj, Barbara Strojny, Daniel Młocicki
Helminths and their products can suppress the host immune response to escape host defense mechanisms and establish chronic infections. Current studies indicate that macrophages play a key role in the immune response to pathogen invasion. They can be polarized into two distinct phenotypes: M1 and M2. The present paper examines the impact of the adult Hymenolepis diminuta (HD) tapeworm and its excretory/secretory products (ESP) on THP-1 macrophages. Monocytes were differentiated into macrophages and cultured with a living parasite or its ESP...
2017: Frontiers in Immunology
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