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Nandini Sen, Phillip Sung, Arjun Panda, Ann M Arvin
Both type I and type II interferons (IFNs) have been implicated in the host defense against varicella zoster virus (VZV), a common human herpesvirus that causes varicella and zoster. The purpose of this study was to compare their contributions to the control of VZV replication, to identify the signaling pathways that are critical for mediating their antiviral activity, and to define mechanisms by which the virus counteracts their effects. IFNγ was much more potent than IFNα in blocking VZV infection, which was associated with a differential induction of the interferon regulatory factor (IRF) proteins, IRF1 and IRF9, respectively...
August 8, 2018: Journal of Virology
Carlos Carballo, Evangelia G Chronopoulou, Sofia Letsiou, Claudia Maya, Nikolaos E Labrou, Carlos Infante, Deborah M Power, Manuel Manchado
The microalgae are an important source of bioactive molecules including β-glucans that can be used as immunostimulants in aquaculture. In the present study, the antioxidant capacity, cytotoxicity and immunomodulatory activity of a chrysolaminarin-enriched extract obtained from the diatom Phaeodactylum tricornutum was evaluated. The extract showed a higher total antioxidant activity as determined by ORAC and FRAP assays and a lower DPPH scavenging activity than particulate yeast-β-glucan. The cytotoxicity test indicated that extract concentrations higher than 0...
July 28, 2018: Fish & Shellfish Immunology
Zhenyu Zhong, Shuang Liang, Elsa Sanchez-Lopez, Feng He, Shabnam Shalapour, Xue-Jia Lin, Jerry Wong, Siyuan Ding, Ekihiro Seki, Bernd Schnabl, Andrea L Hevener, Harry B Greenberg, Tatiana Kisseleva, Michael Karin
Dysregulated NLRP3 inflammasome activity results in uncontrolled inflammation, which underlies many chronic diseases. Although mitochondrial damage is needed for the assembly and activation of the NLRP3 inflammasome, it is unclear how macrophages are able to respond to structurally diverse inflammasome-activating stimuli. Here we show that the synthesis of mitochondrial DNA (mtDNA), induced after the engagement of Toll-like receptors, is crucial for NLRP3 signalling. Toll-like receptors signal via the MyD88 and TRIF adaptors to trigger IRF1-dependent transcription of CMPK2, a rate-limiting enzyme that supplies deoxyribonucleotides for mtDNA synthesis...
August 2018: Nature
Yaqian Li, Huilin Li, Na Su, Dejian Liu, Rui Luo, Hui Jin
DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41), a receptor belonging to DExD/H-box helicase family, acts as an intracellular DNA sensor and induces type I IFN production in mammals and fish. However, the function of avian DDX41 in innate immune response is still unknown. In this study, the full-length duck DDX41 (duDDX41) cDNA sequence was cloned for the first time and encoded a putative protein of 618 amino acid residues which showed the high sequence similarity with both zebra finch and chicken DDX41s...
July 17, 2018: Developmental and Comparative Immunology
Yongxiang Liu, Xiaoxiao Liu, Hongtao Kang, Xiaoliang Hu, Jiasen Liu, Jin Tian, Liandong Qu
Interferons (IFNs) can inhibit most, if not all, viral infections by eliciting the transcription of hundreds of interferon-stimulated genes (ISGs). Feline calicivirus (FCV) is a highly contagious pathogen of cats and a surrogate for Norwalk virus. Interferon efficiently inhibits the replication of FCV, but the mechanism of the antiviral activity is poorly understood. Here, we evaluated the anti-FCV activity of ten ISGs, whose antiviral activities were previously reported. The results showed that interferon regulatory factor 1 (IRF1) can significantly inhibit the replication of FCV, whereas the other ISGs tested in this study failed...
2018: BioMed Research International
Yunxia Liu, Yuqiang Cheng, Wenya Shan, Jingjiao Ma, Hengan Wang, Jianhe Sun, Yaxian Yan
Interferon regulatory factors (IRFs) is an important family for IFN expression regulating while viral infection. IRF1, IRF3, and IRF7 are the primary regulators that trigger type I IFN response in mammals. However, IRF3, which has been identified as the most critical regulator in mammals, is absent in chickens, and it is unknown whether IRF1 is involved in type I IFN signaling pathways in IRF3-deficient chicken cells. Here, we identified chicken IRF1 (chIRF1) as a critical IFN-β mediator in response to viral infection...
July 5, 2018: Developmental and Comparative Immunology
Jan-Dirk Haeger, Christian Loch, Christiane Pfarrer
INTRODUCTION: Uterine glands (UG) are crucial for the establishment of ruminant pregnancy and influenced (orchestrated manner) by estrogen (E2 ), progesterone (P4 ) and interferon tau (IFNτ). In the study we established a bovine endometrial glandular cell line (BGEC) and tested its functional reactivity (signaling) to IFNτ. METHODS: BGEC was characterized by light microscopy (LM), epithelial markers (ezrin, CK18) [immunofluorescence (IF)/immunohistochemistry (IHC)] and ultrastructure (TEM/SEM) (apical microvilli)...
July 2018: Placenta
Kosuke Zenke, Masashi Muroi, Ken-Ichi Tanamoto
The signal transducer and activator of transcription 1 (STAT1), a pivotal transcription factor in Janus kinase (JAK)-STAT signaling, regulates the expression of a wide range of immune-related genes, including interferon (IFN) regulatory factor 1 (IRF1). In this study, we found that IRF1 could induce STAT1 phosphorylation and in turn STAT1 activation. When IRF1 was transiently expressed in HEK293 cells, STAT1 phosphorylated at Y701, dimerized and bound to an oligonucleotide containing a gamma-activated sequence (GAS) derived from the IRF1 promoter...
June 12, 2018: Immunology and Cell Biology
Agata Michalska, Katarzyna Blaszczyk, Joanna Wesoly, Hans A R Bluyssen
Interferon (IFN)-I and IFN-II both induce IFN-stimulated gene (ISG) expression through Janus kinase (JAK)-dependent phosphorylation of signal transducer and activator of transcription (STAT) 1 and STAT2. STAT1 homodimers, known as γ-activated factor (GAF), activate transcription in response to all types of IFNs by direct binding to IFN-II activation site (γ-activated sequence)-containing genes. Association of interferon regulatory factor (IRF) 9 with STAT1-STAT2 heterodimers [known as interferon-stimulated gene factor 3 (ISGF3)] or with STAT2 homodimers (STAT2/IRF9) in response to IFN-I, redirects these complexes to a distinct group of target genes harboring the interferon-stimulated response element (ISRE)...
2018: Frontiers in Immunology
Xiumei Chen, Yongfeng Lai, Xicheng Song, Jinying Wu, Li Wang, Hua Zhang, Zhonglu Liu, Yan Wang
Chronic pharyngitis is characterized as a common inflammation of the pharyngeal mucosa, and anti-inflammatory medications are the common treatment to relieve it. Polysacharides of Citrus grandis L. Osbeck (PCG) and luteolin have been reported to have anti-inflammatory activities. In this study, the protective effects of PCG and luteolin on chronic pharyngitis are evaluated and the underlying mechanisms are explored. PCG and luteolin are administrated to animal models with granuloma, ear edema and chronic pharyngitis and the effects of PCG and luteolin on disease severity are evaluated...
January 2018: International Journal of Immunopathology and Pharmacology
Yoshihiko Hagiwara, Hiro Sato, Tiara Bunga Mayang Permata, Atsuko Niimi, Motohiro Yamauchi, Takahiro Oike, Takashi Nakano, Atsushi Shibata
Programmed cell death-1 (PD-1) and its ligand (programmed death-ligand 1, PD-L1) are key factors that regulate a cytotoxic immune reaction. Anti-PD-1 therapy provides significant clinical benefits for patients with cancer, even those with advanced-stage cancer. We have recently demonstrated that DNA damage signaling from DNA double-strand breaks (DSBs) promotes PD-L1 upregulation in cancer cells. In the present study, we aimed to investigate PD-L1 expression in primary normal human dermal fibroblasts (NHDFs) in response to DSBs...
August 2018: Human Immunology
Manman Liu, Junli Liu, Shumeng Hao, Ping Wu, Xiaoyan Zhang, Yichuan Xiao, Gengru Jiang, Xinfang Huang
Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells...
May 17, 2018: Clinical Rheumatology
Irati Romero-Garmendia, Koldo Garcia-Etxebarria, Hector Hernandez-Vargas, Izortze Santin, Amaia Jauregi-Miguel, Leticia Plaza-Izurieta, Marie-Pierre Cros, Maria Legarda, Iñaki Irastorza, Zdenko Herceg, Nora Fernandez-Jimenez, Jose Ramon Bilbao
The aim of this study was to construct celiac co-expression patterns at a whole genome level and to identify transcription factors (TFs) that could drive the gliadin-related changes in coordination of gene expression observed in celiac disease (CD). Differential co-expression modules were identified in the acute and chronic responses to gliadin using expression data from a previous microarray study in duodenal biopsies. Transcription factor binding site (TFBS) and Gene Ontology (GO) annotation enrichment analyses were performed in differentially co-expressed genes (DCGs) and selection of candidate regulators was performed...
May 10, 2018: Genes
Mohamed Abou El Hassan, Katherine Huang, Zhaodong Xu, Tao Yu, Rod Bremner
Transcriptional activators bind DNA and recruit cofactors to modify chromatin. The extent to which these two events are separable is unclear. Here, using a custom ChIP tiling array to map chromatin modifications, we show that interferon-γ-induced DNA binding of signal transducer and activator of transcription 1 (STAT1), typically associated with the transcription factor interferon regulatory factor 1 (IRF1), causes histone acetylation (H3ac, H4ac). In contrast, among IRF1 sites lacking concomitant STAT1 recruitment, only 25% underwent inducible histone acetylation, 31% exhibited constitutive histone acetylation, and 44% had no histone acetylation...
June 29, 2018: Journal of Biological Chemistry
Cheng-Yan Mou, Yang Wang, Qi-Ya Zhang, Fan-Xiang Gao, Zhi Li, Jin-Feng Tong, Li Zhou, Jian-Fang Gui
Interferon (IFN) system plays a vital role in the first line of defense against viruses. In this study, we first identified multiple transcripts of 15 IFN system genes, including PRRs (TLR2, TLR3, RIG-I, and LGP2), PRR-mediated IFN signal pathway (MyD88, MITA, and MAVS), IFN regulatory factors (IRF1, IRF3, IRF7, and IRF9), IFNs (IFNφ1 and IFNφ3), and ISGs (Mx and viperin), and one transcript of TLR9 in de novo transcriptome assembly data of gibel carp head-kidney. Multiple nucleotide alignments and phylogenetic analysis of common region showed that the transcripts of every of the 15 IFN system genes were classified into two homologs with distinctly divergent sequences, indicating that hexaploid gibel carp may be an allopolyploid...
September 2018: Developmental and Comparative Immunology
Corey L Campbell, Aaron T Phillips, Amber Rico, Amanda McGuire, Tawfik A Aboellail, Sandra Quackenbush, Ken E Olson, Tony Schountz
New World arenaviruses cause fatal hemorrhagic disease in South America. Pirital virus (PIRV), a mammarenavirus hosted by Alston’s cotton rat ( Sigmodon alstoni ), causes a disease in Syrian golden hamsters ( Mesocricetus auratus ) (biosafety level-3, BSL-3) that has many pathologic similarities to the South American hemorrhagic fevers (BSL-4) and, thus, is considered among the best small-animal models for human arenavirus disease. Here, we extend in greater detail previously described clinical and pathological findings in Syrian hamsters and provide evidence for a pro-inflammatory macrophage response during PIRV infection...
May 2, 2018: Viruses
Kenneth J Dery, Craig Silver, Lu Yang, John E Shively
The adhesion protein carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is widely expressed in epithelial cells as a short cytoplasmic isoform (S-iso) and in leukocytes as a long cytoplasmic isoform (L-iso) and is frequently silenced in cancer by unknown mechanisms. Previously, we reported that interferon response factor 1 (IRF1) biases alternative splicing (AS) to include the variable exon 7 (E7) in CEACAM1, generating long cytoplasmic isoforms. We now show that IRF1 and a variant of heterogeneous nuclear ribonucleoprotein L (Lv1) coordinately silence the CEACAM1 gene...
June 15, 2018: Journal of Biological Chemistry
Tina Cascone, Jodi A McKenzie, Rina M Mbofung, Simone Punt, Zhe Wang, Chunyu Xu, Leila J Williams, Zhiqiang Wang, Christopher A Bristow, Alessandro Carugo, Michael D Peoples, Lerong Li, Tatiana Karpinets, Lu Huang, Shruti Malu, Caitlin Creasy, Sara E Leahey, Jiong Chen, Yuan Chen, Helen Pelicano, Chantale Bernatchez, Y N Vashisht Gopal, Timothy P Heffernan, Jianhua Hu, Jing Wang, Rodabe N Amaria, Levi A Garraway, Peng Huang, Peiying Yang, Ignacio I Wistuba, Scott E Woodman, Jason Roszik, R Eric Davis, Michael A Davies, John V Heymach, Patrick Hwu, Weiyi Peng
Adoptive T cell therapy (ACT) produces durable responses in some cancer patients; however, most tumors are refractory to ACT and the molecular mechanisms underlying resistance are unclear. Using two independent approaches, we identified tumor glycolysis as a pathway associated with immune resistance in melanoma. Glycolysis-related genes were upregulated in melanoma and lung cancer patient samples poorly infiltrated by T cells. Overexpression of glycolysis-related molecules impaired T cell killing of tumor cells, whereas inhibition of glycolysis enhanced T cell-mediated antitumor immunity in vitro and in vivo...
May 1, 2018: Cell Metabolism
Jianzhou Chen, Bostjan Markelc, Jakob Kaeppler, Vivian M L Ogundipe, Yunhong Cao, W Gillies McKenna, Ruth J Muschel
PURPOSE: To investigate the induction of type III interferons (IFNs) in human cancer cells by gamma-rays. METHODS AND MATERIALS: Type III IFN expression in human cancer cell lines after gamma-ray irradiation in vitro was assessed by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Signaling pathways mediating type III IFN induction were examined by a variety of means, including immunoblotting, flow cytometry, confocal imaging, and reverse transcription-quantitative polymerase chain reaction...
May 1, 2018: International Journal of Radiation Oncology, Biology, Physics
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Maki Wakamiya, Roberto P Garofalo, Allan R Brasier
Lower respiratory tract infection with respiratory syncytial virus (RSV) produces profound inflammation. Despite an understanding of the role of adaptive immunity in RSV infection, the identity of the major sentinel cells initially triggering inflammation is controversial. Here we evaluate the role of nonciliated secretoglobin ( Scgb1a1 )-expressing bronchiolar epithelial cells in RSV infection. Mice expressing a tamoxifen (TMX)-inducible Cre recombinase-estrogen receptor fusion protein (CreERTM) knocked into the Scgb1a1 locus were crossed with mice that harbor a RelA conditional allele ( RelAfl ), with loxP sites flanking exons 5 to 8 of the Rel homology domain...
June 1, 2018: Journal of Virology
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