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Interferon regulatory factor

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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
#1
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, absence of STAT1, STAT2 or IRF9 exacerbates neurological disease in transgenic mice with CNS-production of IFN-Ι. 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)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209510/microarray-and-transcription-binding-site-analysis-reveals-that-melatonin-attenuates-immune-responses-and-modulates-actin-rearrangement-in-macrophages
#2
Miki Kadena, Yutaro Kumagai, Alexis Vandenbon, Hitomi Matsushima, Haruka Fukamachi, Noboru Maruta, Hideo Kataoka, Takafumi Arimoto, Hirobumi Morisaki, Takahiro Funatsu, Hirotaka Kuwata
Melatonin produced by the pineal gland suppresses inflammatory responses in innate immune cells. However, the mechanism of how melatonin affects inflammatory gene regulation remains unclear. Here we performed comprehensive microarray analysis combined with transcription factor binding site (TFBS) analysis using LPS-induced mouse macrophages to investigate the effect of melatonin treatment. The results showed that melatonin preferentially downregulated interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) related signaling...
February 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28203525/microrna-520c-enhances-cell-proliferation-migration-and-invasion-by-suppressing-irf2-in-gastric-cancer
#3
Ying-Ru Li, Li-Qiang Wen, Yang Wang, Tai-Cheng Zhou, Ning Ma, Ze-Hui Hou, Zhi-Peng Jiang
Dysregulation of microRNA (miRNA) is actively involved in the development and progression of gastric cancer (GC). MiR-520c was previously found to be overexpressed in GC specimens and cells. However, the clinical significance of miR-520c and its biological function in GC remain largely unknown. Here, we found that miR-520c expression in GC tissues was significantly increased compared to normal adjacent gastric tissues. Its increased level was prominently correlated with poor clinical parameters and prognosis of GC patients...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28202761/the-long-noncoding-rna-neat1-exerts-anti-hantaviral-effects-by-acting-as-a-positive-feedback-for-rig-i-signaling
#4
Hongwei Ma, Peijun Han, Wei Ye, Hesong Chen, Xuyang Zheng, Linfeng Cheng, Liang Zhang, Lan Yu, Xing'an Wu, Zhikai Xu, Yingfeng Lei, Fanglin Zhang
Hantavirus infection, which causes zoonotic diseases with a high mortality rate in humans, has long been a global public health concern. Over the past decades, accumulating evidence suggests that long noncoding RNAs (lncRNAs) play key regulatory roles in innate immunity. However, the involvement of host lncRNAs in hantaviral control remains uncharacterized. In this study, we identified the lncRNA, NEAT1, as a vital antiviral modulator. NEAT1 was dramatically upregulated after Hantaan virus (HTNV) infection, whereas its downregulation in vitro or in vivo delayed host innate immune responses and aggravated HTNV replication...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28197148/avian-interferons-and-their-antiviral-effectors
#5
REVIEW
Diwakar Santhakumar, Dennis Rubbenstroth, Luis Martinez-Sobrido, Muhammad Munir
Interferon (IFN) responses, mediated by a myriad of IFN-stimulated genes (ISGs), are the most profound innate immune responses against viruses. Cumulatively, these IFN effectors establish a multilayered antiviral state to safeguard the host against invading viral pathogens. Considerable genetic and functional characterizations of mammalian IFNs and their effectors have been made, and our understanding on the avian IFNs has started to expand. Similar to mammalian counterparts, three types of IFNs have been genetically characterized in most avian species with available annotated genomes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28196914/the-host-microrna-mir-301a-blocks-the-irf1-mediated-neuronal-innate-immune-response-to-japanese-encephalitis-virus-infection
#6
Bibhabasu Hazra, Kanhaiya Lal Kumawat, Anirban Basu
Effective recognition of viral components and the subsequent stimulation of the production of type I interferons (IFNs) is crucial for the induction of host antiviral immunity. The failure of the host to efficiently produce type I IFNs in response to infection by the Japanese encephalitis virus (JEV) is linked with an increased probability for the disease to become lethal. JEV is a neurotropic virus of the Flaviviridae family that causes encephalitis in humans. JEV infection is regulated by several host factors, including microRNAs, which are conserved noncoding RNAs that participate in various physiological and pathological processes...
February 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28196779/the-role-of-type-i-interferons-in-innate-and-adaptive-immunity-against-viruses-in-atlantic-salmon
#7
Børre Robertsen
Type I IFNs (IFN-I) are cytokines, which play a crucial role in innate and adaptive immunity against viruses of vertebrates. In essence, IFN-I are induced and secreted upon host cell recognition of viral nucleic acids and protect other cells against infection by inducing antiviral proteins. Atlantic salmon possesses an extraordinary repertoire of IFN-I genes encompassing at least six different classes (IFNa, IFNb, IFNc, IFNd, IFNe and IFNf) most of which are encoded by several genes. This review describes recent research on the functions of salmon IFNa, IFNb, IFNc and IFNd...
February 11, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28192879/knockdown-of-irf3-inhibits-extracellular-matrix-expression-in-keloid-fibroblasts
#8
Yi Zhang, Li Zhang, Xiao-Hua Lin, Zhi-Ming Li, Qi-Yu Zhang
Keloid is a pathologic fibro-proliferative disorder and is characterized by hyper-proliferation of fibroblasts and excess extracellular matrix (ECM) deposition. Interferon regulatory factor 3 (IRF3) is a member of the interferon-regulatory factor (IRF) family and has been shown to play a critical modulator in the progression of fibrosis. However, the function of IRF3 in dermal fibrosis remains unclear. Thus, in this study, we investigated the effects of IRF3 on keloid-derived fibroblasts (KFs) proliferation and ECM expression, and explored the underlying mechanism...
February 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28188292/cytosolic-dna-promotes-signal-transducer-and-activator-of-transcription-3-stat3-phosphorylation-by-tank-binding-kinase-1-tbk1-to-restrain-stat3-activity
#9
Hung-Ching Hsia, Jessica E Hutti, Albert S Baldwin
Cytosolic DNA can elicit beneficial as well as undesirable immune responses. For example, viral or microbial DNA triggers cell-intrinsic immune responses to defend against infections, whereas aberrant cytosolic accumulation of self-DNA results in pathological conditions, such as autoimmunity. Given the importance of these DNA-provoked responses, a better understanding of their molecular mechanisms is needed. Cytosolic DNA engages stimulator of interferon genes (STING) to activate TANK-binding kinase 1 (TBK1), which subsequently phosphorylates the transcription factor interferon regulatory factor 3 (IRF3) to promote interferon expression...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28186653/progression-of-cutaneous-plasmacytoma-to-plasma-cell-leukemia-in-a-dog
#10
Emily D Rout, Alba Maria M Shank, Angharad H K Waite, Andrea Siegel, Anne C Avery, Paul R Avery
A 5-year-old male neutered Bernese Mountain Dog was presented for cutaneous plasmacytoma, which was treated by surgical excision. Four months later, the dog developed multiple skin masses, hyphema, pericardial and mild bicavitary effusions, myocardial masses, and marked plasmacytosis in the peripheral blood. Circulating plasma cells expressed CD34 and MHC class II by flow cytometry. Immunocytochemistry demonstrated that these cells were strongly positive for multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM-1) and weakly to moderately positive for Pax5...
February 10, 2017: Veterinary Clinical Pathology
https://www.readbyqxmd.com/read/28185859/association-of-irf5-polymorphisms-with-increased-risk-for-systemic-lupus-erythematosus-in-population-of-crete-a-southern-eastern-european-greek-island
#11
M I Zervou, J M Dorschner, Y Ghodke-Puranik, D T Boumpas, T B Niewold, G N Goulielmos
Interferon regulatory factor 5 (IRF5) regulates type I interferon (IFN)-responsive genes, and has been one of the most consistently associated genes with systemic lupus erythematosus (SLE). We sought to investigate whether IRF5 haplotypes are associated with risk for SLE in the genetically homogeneous Greek population of the island of Crete, as well as whether these haplotypes are associated with increased type I IFN. 322 SLE patients and 247 healthy controls from Crete were genotyped for rs2004640, rs3807306, rs10488631 and rs2280714 SNPs of IRF5 gene by using Taqman primer-probe sets...
February 6, 2017: Gene
https://www.readbyqxmd.com/read/28184969/augmented-anti-tumor-activity-of-nk-92-cells-expressing-chimeric-receptors-of-tgf-%C3%AE-r-ii-and-nkg2d
#12
Zhongjuan Wang, Linghua Guo, Yuan Song, Yinsheng Zhang, Dandan Lin, Bo Hu, Yu Mei, Dedy Sandikin, Haiyan Liu
The capacity of natural killer (NK) cells to kill tumor cells without specific antigen recognition provides an advantage over T cells and makes them potential effectors for tumor immunotherapy. However, the efficacy of NK cell adoptive therapy can be limited by the immunosuppressive tumor microenvironment. Transforming growth factor-β (TGF-β) is a potent immunosuppressive cytokine that can suppress NK cell function. To convert the suppressive signal induced by TGF-β to an activating signal, we genetically modified NK-92 cells to express a chimeric receptor with TGF-β type II receptor extracellular and transmembrane domains and the intracellular domain of NK cell-activating receptor NKG2D (TN chimeric receptor)...
February 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28184222/canonical-and-non-canonical-aspects-of-jak-stat-signaling-lessons-from-interferons-for-cytokine-responses
#13
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/28181039/irf3-inhibits-neutrophil-recruitment-in-mice-infected-with-pseudomonas-aeruginosa
#14
Zhenghao Piao, Haiying Yuan, Cuili Wang, Liyun Shi
Pseudomonas aeruginosa is the major cause of morbidity and mortality in patients with ventilator-associated pneumonia. Interferon regulatory factor 3 (IRF3) is a transcription factor that plays an important role in the immune response to viral infection via the IRF3/IFN-β signaling pathway. Controversial data exist regarding the role of IRF3 in immune cell recruitment during bacterial infections. IRF3 has been shown to promote neutrophil recruitment and bacterial clearance in mice infected with P. aeruginosa by inducing the production of specific chemokines and cytokines...
February 8, 2017: Inflammation
https://www.readbyqxmd.com/read/28174303/central-regulatory-role-for-sin1-in-interferon-%C3%AE-ifn%C3%AE-signaling-and-generation-of-biological-responses
#15
Barbara Kroczynska, Gavin T Blyth, Robert L Rafidi, Beata Majchrzak-Kita, Lucy Xu, Diana Saleiro, Ewa M Kosciuczuk, Jacek Jemielity, Bing Su, Jessica K Altman, Elizabeth A Eklund, Eleanor H Fish, Leonidas C Platanias
The precise signaling mechanisms by which Type II interferon (IFN) receptors control expression of unique genes to induce biological responses remain to be established. We provide evidence that Sin1, a known element of the mammalian target of rapamycin complex 2 (mTORC2), is required for IFNγ-induced phosphorylation and activation of AKT and that such activation mediates downstream regulation of mTORC1 and its effectors. These events play important roles in the assembly of the translation initiation factor 4F (eIF4F) and mRNA translation of ISGs...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28164410/hypoxia-inducible-microrna-210-regulates-the-dimt1-irf4-oncogenic-axis-in-multiple-myeloma
#16
Sho Ikeda, Akihiro Kitadate, Fumito Abe, Saitoh Hirobumi, Yoshihiro Michishita, Yoshiaki Hatano, Yoshinari Kawabata, Atsushi Kitabayashi, Kazuaki Teshima, Masaaki Kume, Naoto Takahashi, Hiroyuki Tagawa
Multiple myeloma (MM) is characterized by the accumulation of a population of malignant plasma cells within the bone marrow and its microenvironment. A hypoxic niche is located within the microenvironment, which causes myeloma cells to become quiescent, anti-apoptotic, glycolytic, and immature. Cell heterogeneity may be related to distinct gene expression profiles under hypoxic and normoxic conditions. During hypoxia, myeloma cells acquire these phenotypes by downregulating interferon regulatory factor 4 (IRF4), an essential transcription factor in myeloma oncogenesis...
February 6, 2017: Cancer Science
https://www.readbyqxmd.com/read/28164173/tgf-%C3%AE-1-along-with-other-platelet-contents-augments-treg-cells-to-suppress-anti-fviii-immune-responses-in-hemophilia-a-mice
#17
Dipica Haribhai, Xiaofeng Luo, Juan Chen, Shuang Jia, Linzheng Shi, Jocelyn A Schroeder, Hartmut Weiler, Richard H Aster, Martin J Hessner, Jianda Hu, Calvin B Williams, Qizhen Shi
Platelets are a rich source of many cytokines and chemokines including transforming growth factor β 1 (TGF-β1). TGF-β1 is required to convert conventional CD4(+) T (Tconv) cells into induced regulatory T (iTreg) cells that express the transcription factor Foxp3. Whether platelet contents will affect Treg cell properties has not been explored. In this study, we show that unfractionated platelet lysates (pltLys) containing TGF-β1 efficiently induced Foxp3 expression in Tconv cells. The common Treg cell surface phenotype and in vitro suppressive activity of unfractionated pltLys-iTreg cells were similar to those of iTreg cells generated using purified TGF-β1 (purTGFβ-iTreg) cells...
December 13, 2016: Blood Adv
https://www.readbyqxmd.com/read/28159912/identification-of-tbk1-complexes-required-for-the-phosphorylation-of-irf3-and-the-production-of-interferon-b
#18
Siddharth Bakshi, Jordan Taylor, Sam Strickson, Thomas Macartney, Philip Cohen
The double-stranded RNA mimetic poly(I:C) and LPS activate Toll-like Receptor 3 (TLR3) and TLR4, respectively, triggering the activation of TANK-Binding Kinase 1 (TBK1) complexes, the phosphorylation of Interferon Regulatory Factor 3 (IRF3) and transcription of the Interferon b (IFNb) gene. Here, we demonstrate that the TANK-TBK1 and Optineurin (OPTN)-TBK1 complexes control this pathway. The poly(I:C)- or LPS-stimulated phosphorylation of IRF3 at Ser396 and production of IFNb were greatly reduced in bone-marrow-derived macrophages (BMDM) from TANK knock-out (KO) mice crossed to knock-in mice-expressing the ubiquitin-binding-defective OPTN[D477N] mutant...
February 3, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28150813/an-engineered-herpesvirus-activates-dendritic-cells-and-induces-protective-immunity
#19
Yijie Ma, Min Chen, Huali Jin, Bellur S Prabhakar, Tibor Valyi-Nagy, Bin He
Herpes simplex viruses (HSV) are human pathogens that switch between lytic and latent infection. While attenuated HSV is explored for vaccine, the underlying event remains poorly defined. Here we report that recombinant HSV-1 with a mutation in the γ134.5 protein, a virulence factor, stimulates dendritic cell (DC) maturation which is dependent on TANK-binding kinase 1 (TBK1). When exposed to CD11(+) DCs, the mutant virus that lacks the amino terminus of γ134.5 undergoes temporal replication without production of infectious virus...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28149533/tff3-dependent-resistance-of-human-colorectal-adenocarcinoma-cells-ht-29-b6-to-apoptosis-is-mediated-by-mir-491-5p-regulation-of-lncrna-prins
#20
Carlos Hanisch, Jutta Sharbati, Barbara Kutz-Lohroff, Otmar Huber, Ralf Einspanier, Soroush Sharbati
Tumour necrosis factor-α (TNF-α) is a double-edged cytokine associated with pathogenesis of inflammatory-related cancers being also able to induce cancer cell death. In the process of tumour development or metastasis, cancer cells can become resistant to TNF-α. In trefoil factor 3 (TFF3) overexpressing colorectal adenocarcinoma cells (HT-29/B6), we observed enhanced resistance against TNF-α/interferon gamma-induced apoptosis. TFF3 is a secreted small peptide that supports intestinal tissue repair but is also involved in intestinal tumour progression and scattering...
2017: Cell Death Discovery
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