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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
March 17, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28295457/hepatic-ifit3-predicts-interferon-%C3%AE-therapeutic-response-in-patients-of-hepatocellular-carcinoma
#8
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
#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/28278235/a-novel-zika-virus-mouse-model-reveals-strain-specific-differences-in-virus-pathogenesis-and-host-inflammatory-immune-responses
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28250121/porcine-deltacoronavirus-nsp5-antagonizes-type-i-interferon-signaling-by-cleaving-stat2
#13
Xinyu Zhu, Dang Wang, Junwei Zhou, Ting Pan, Jiyao Chen, Yuting Yang, Mengting Lv, Xu Ye, Guiqing Peng, Liurong Fang, Shaobo Xiao
Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus. The first outbreak of PDCoV was announced from the United States in 2014, followed by reports in Asia. The nonstructural protein nsp5 is a 3C-like protease of coronavirus and our previous study showed that PDCoV nsp5 inhibits type I interferon (IFN) production. In this study, we found that PDCoV nsp5 significantly inhibited IFN-stimulated response element (ISRE) promoter activity and transcription of IFN-stimulated genes (ISGs), suggesting that PDCoV nsp5 also suppresses IFN signaling...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28242623/type-i-interferon-enhanced-il-10-expression-in-human-cd4-t-cells-is-regulated-by-stat3-stat2-and-batf-transcription-factors
#14
Umeshree Govender, Béatrice Corre, Yasmine Bourdache, Sandra Pellegrini, Frédérique Michel
Type I IFN can exert pro- and anti-inflammatory activities in the immune system. Here, we have investigated the mechanism by which IFN-α enhances early expression of the anti-inflammatory cytokine IL-10 in human CD45RA(+)CD4(+) T cells. With the use of transcriptomic and biochemical approaches, we found distinct and combined contributions of the IFN and the TCR signaling pathways to the induction of STAT1/2/3 and the basic leucine zipper activating transcription factor-like (BATF) family members. Moreover, IFN-induced STAT3 phosphorylation was prolonged by the TCR response, whereas IFN-induced STAT2 phosphorylation was of long duration...
February 27, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28226265/alterations-of-ubiquitin-related-proteins-in-the-pathology-and-development-of-schizophrenia-evidence-from-human-and-animal-studies
#15
Jessica L Andrews, Frederic J Goodfellow, Natalie Matosin, Mollie K Snelling, Kelly A Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia...
January 18, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28213522/type-i-interferon-regulated-gene-expression-and-signaling-in-murine-mixed-glial-cells-lacking-signal-transducers-and-activators-of-transcription-1-or-2-or-interferon-regulatory-factor-9
#16
Wen Li, Markus J Hofer, Pattama Songkhunawej, So Ri Jung, Dale Hancock, Gareth Denyer, Iain L Campbell
Type I interferons (IFN-I) are critical in antimicrobial and antitumor defense. Although IFN-I signal via the interferon-stimulated gene factor 3 (ISGF3) complex consisting of STAT1, STAT2, and IRF9, IFN-I can mediate significant biological effects via ISGF3-independent pathways. For example, the absence of STAT1, STAT2, or IRF9 exacerbates neurological disease in transgenic mice with CNS production of IFN-I. Here we determined the role of IFN-I-driven, ISGF3-independent signaling in regulating global gene expression in STAT1-, STAT2-, or IRF9-deficient murine mixed glial cell cultures (MGCs)...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28199372/endometrial-factors-similarly-induced-by-ifnt2-and-ifntc1-through-transcription-factor-foxs1
#17
Kazuya Kusama, Rulan Bai, Keigo Nakamura, Sayaka Okada, Jiro Yasuda, Kazuhiko Imakawa
In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs)...
2017: PloS One
https://www.readbyqxmd.com/read/28184222/canonical-and-non-canonical-aspects-of-jak-stat-signaling-lessons-from-interferons-for-cytokine-responses
#18
REVIEW
Andrea Majoros, Ekaterini Platanitis, Elisabeth Kernbauer-Hölzl, Felix Rosebrock, Mathias Müller, Thomas Decker
Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction mediates cytokine responses. Canonical signaling is based on STAT tyrosine phosphorylation by activated JAKs. Downstream of interferon (IFN) receptors, activated JAKs cause the formation of the transcription factors IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1, STAT2 and interferon regulatory factor 9 (IRF9) subunits, and gamma interferon-activated factor (GAF), a STAT1 homodimer. In recent years, several deviations from this paradigm were reported...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28165510/stat2-is-an-essential-adaptor-in-usp18-mediated-suppression-of-type-i-interferon-signaling
#19
Kei-Ichiro Arimoto, Sara Löchte, Samuel A Stoner, Christoph Burkart, Yue Zhang, Sayuri Miyauchi, Stephan Wilmes, Jun-Bao Fan, Jürgen J Heinisch, Zhi Li, Ming Yan, Sandra Pellegrini, Frédéric Colland, Jacob Piehler, Dong-Er Zhang
Type I interferons (IFNs) are multifunctional cytokines that regulate immune responses and cellular functions but also can have detrimental effects on human health. A tight regulatory network therefore controls IFN signaling, which in turn may interfere with medical interventions. The JAK-STAT signaling pathway transmits the IFN extracellular signal to the nucleus, thus resulting in alterations in gene expression. STAT2 is a well-known essential and specific positive effector of type I IFN signaling. Here, we report that STAT2 is also a previously unrecognized, crucial component of the USP18-mediated negative-feedback control in both human and mouse cells...
March 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28164560/the-study-of-immune-response-in-pbmc-of-chb-patients-treated-with-ifn-%C3%AE-and-3-tc-in-vitro
#20
Hao Zhang, Zi-Shu Guan, Shi-He Guan, Kai Yang, Ying Pan, Yuan-Yuan Wu, Ai-Hua Wang, Bei-Bei Sun, Jie Hou, Xuan-Xuan Mu, Yu-Feng Gao, Wei-Sheng Cheng
BACKGROUND: The primary aim of this study is to measure the JAK-STAT signaling in HBV infected peripheral blood mononuclear cells (PBMCs) stimulated by IFN-α and 3-TC and explore the influence of HBV to the JAKSTAT signaling pathways. METHODS: PBMCs were separated from healthy volunteers and patients who had not received any treatment with chronic hepatitis B. PBMCs were divided into the control group, IFN-α stimulation group, Lamivudine stimulation group, and combined treatment group...
December 1, 2016: Clinical Laboratory
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