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Jiawen Qian, Chen Wang, Bo Wang, Jiao Yang, Yuedi Wang, Feifei Luo, Junying Xu, Chujun Zhao, Ronghua Liu, Yiwei Chu
BACKGROUND: PD-L1 is an immune inhibitory receptor ligand that leads to T cell dysfunction and apoptosis by binding to its receptor PD-1, which works in braking inflammatory response and conspiring tumor immune evasion. However, in gliomas, the cause of PD-L1 expression in the tumor microenvironment is not yet clear. Besides, auxiliary biomarkers are urgently needed for screening possible responsive glioma patients for anti-PD-1/PD-L1 therapies. METHODS: The distribution of tumor-infiltrating T cells and PD-L1 expression was analyzed via immunofluorescence in orthotopic murine glioma model...
October 17, 2018: Journal of Neuroinflammation
Liang-Che Chang, Tzu-Ping Chen, Wei-Ke Kuo, Chung-Ching Hua
Introduction: The expression of programmed death 1 (PD1) and programmed death ligand 1 (PDL1) can be induced by the interferon (IFN)/signal transducer and activator of transcription (STAT) pathway. The PD1/PDL1 reverse signaling can activate the eukaryotic translation initiation factor 2 (eIF2 α )/activating transcription factor 4 (ATF4) pathway which in turn regulates the expression of IFN regulatory factor (IRF) 7 and IFN α . The eIF2 α /ATF4 pathway is responsible for the integrated stress response (ISR) of unfolded protein response (UPR) which can affect immune cell function in tumor microenvironment...
2018: Disease Markers
Viviana Annibali, Renato Umeton, Antonia Palermo, Martina Severa, Marilena Paola Etna, Simona Giglio, Silvia Romano, Michela Ferraldeschi, Maria Chiara Buscarinu, Andrea Vecchione, Anita Annese, Claudia Policano, Rosella Mechelli, Raffaella Pizzolato Umeton, Arianna Fornasiero, Daniela Francesca Angelini, Gisella Guerrera, Luca Battistini, Eliana Marina Coccia, Marco Salvetti, Giovanni Ristori
Several evidences emphasize B-cell pathogenic roles in multiple sclerosis (MS). We performed transcriptome analyses on peripheral B cells from therapy-free patients and age/sex-matched controls. Down-regulation of two transcripts (interferon response factor 1-IRF1, and C-X-C motif chemokine 10-CXCL10), belonging to the same pathway, was validated by RT-PCR in 26 patients and 21 controls. IRF1 and CXCL10 transcripts share potential seeding sequences for hsa-miR-424, that resulted up-regulated in MS patients...
November 15, 2018: Journal of Neuroimmunology
Maikel L Colli, Jessica L E Hill, Laura Marroquí, Jessica Chaffey, Reinaldo S Dos Santos, Pia Leete, Alexandra Coomans de Brachène, Flavia M M Paula, Anne Op de Beeck, Angela Castela, Lorella Marselli, Lars Krogvold, Knut Dahl-Jorgensen, Piero Marchetti, Noel G Morgan, Sarah J Richardson, Décio L Eizirik
BACKGROUND: Antibodies targeting PD-1 and its ligand PDL1 are used in cancer immunotherapy but may lead to autoimmune diseases, including type 1 diabetes (T1D). It remains unclear whether PDL1 is expressed in pancreatic islets of people with T1D and how is it regulated. METHODS: The expression of PDL1, IRF1, insulin and glucagon was evaluated in samples of T1D donors by immunofluorescence. Cytokine-induced PDL1 expression in the human beta cell line, EndoC-βH1, and in primary human pancreatic islets was determined by real-time RT-PCR, flow cytometry and Western blot...
September 27, 2018: EBioMedicine
Kexin Hua, Yaqian Li, Hongjian Chen, Jiamin Ni, Dingren Bi, Rui Luo, Hui Jin
TRAF family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) serves as hub molecule at the crossroad of multiple signaling pathways of type I interferon (IFN) induction. The importance of TBK1 in innate immunity has been demonstrated in mammalian, however the characterization and function of TBK1 in avian remains largely unknown. In this study, we cloned duck TBK1 (duTBK1) from duck embryo fibroblasts (DEFs) for the first time, which encoded 729 amino acids and had a high amino acid identity with goose and cormorant TBK1s...
September 27, 2018: Cytokine
Tiantian Gu, Lu Lu, Chen An, Yu Zhang, Xinsheng Wu, Qi Xu, Guohong Chen
Ubiquitin-specific protease 18 (USP18) plays an important role in regulating type I interferon (IFN) signaling in innate immunity, and has a crucial impact on the IFN therapeutic effect. Although significant progress has been made in elucidating USP18 function in mammals, the role of USP18 in ducks (duUSP18) remains poorly understood. In this study, we cloned the USP18 gene from white crested ducks by reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of complementary DNA (cDNA) ends...
September 7, 2018: Journal of Cellular Physiology
Jinsheng Liang, Ying Cui, Yuhuan Meng, Xingsong Li, Xueping Wang, Wanli Liu, Lizhen Huang, Hongli Du
Transcription factors are recognized as the key regulators of gene expression. However, the changes in the correlation of transcription factors and their target genes between normal and tumor tissues are usually ignored. In this research, we used mRNA expression profile data from The Cancer Genome Atlas which included 5726 samples across 11 major human cancers to perform co-expression analysis by the Pearson correlation coefficients. Then, integrating 81,357 pairs of transcription factors and target genes from transcription factors databases to find out the changes in the co-expression correlation of these gene pairs from normal to tumor tissues...
September 24, 2018: Functional & Integrative Genomics
Atsushi Shiozaki, Yosuke Ariyoshi, Daisuke Iitaka, Toshiyuki Kosuga, Hiroki Shimizu, Michihiro Kudou, Tomoki Konishi, Katsutoshi Shoda, Tomohiro Arita, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Mitsuo Kishimoto, Eiichi Konishi, Yoshinori Marunaka, Daisuke Ichikawa, Eigo Otsuji
BACKGROUND: Recent studies have described important roles for the sodium iodide symporter (NIS) in tumor behavior. The objectives of the present study were to investigate the role of NIS in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in gastric cancer (GC). METHODS: In human GC cell lines, knockdown experiments were conducted using NIS siRNA, and the effects on proliferation, survival, and cellular movement were analyzed...
September 6, 2018: Gastric Cancer
Kazumi Ebine, Krishan Kumar, Thao N Pham, Mario A Shields, Katharine A Collier, Meng Shang, Brian T DeCant, Raul Urrutia, Rosa F Hwang, Sam Grimaldo, Daniel R Principe, Paul J Grippo, David J Bentrem, Hidayatullah G Munshi
The fibrotic reaction is a characteristic feature of human pancreatic ductal adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation of pancreatic stellate cells (PSCs), which are key regulators of fibrosis in vivo. While there is increasing interest in the regulation of PD-L1 expression in cancer and immune cells, the expression and regulation of PD-L1 in other stromal cells, such as PSCs, has not been fully evaluated. Here we show that PSCs in vitro express higher PD-L1 mRNA and protein levels compared to the levels present in PDAC cells...
September 5, 2018: Scientific Reports
Peiqi Wan, Xiaojv Chi, Qiang Du, Jing Luo, Xiao Cui, Kun Dong, Yan Bing, Caroline Heres, David A Geller
Interferon regulatory factor 1 (IRF1) has been found to serve as a tumor suppressor in cholangiocarcinoma, and enabled prediction of clinical progression and prognosis in our previous study. The objective of the current study is to screen and identify valuable microRNAs (miR), which target IRF1 to regulate cholangiocarcinoma cell proliferation, migration, and invasion. High expression of miR-383 was observed in cholangiocarcinoma tissues and cells. Meanwhile, we found the predicted binding site of miR-383 on the IRF1 3'-untranslated region (3'-UTR) according to the miR target database...
August 26, 2018: Journal of Cellular Biochemistry
Priya Luthra, Jacinth Naidoo, Colette A Pietzsch, Sampriti De, Sudip Khadka, Manu Anantpadma, Caroline G Williams, Megan R Edwards, Robert A Davey, Alexander Bukreyev, Joseph M Ready, Christopher F Basler
Specific host pathways that may be targeted therapeutically to inhibit the replication of Ebola virus (EBOV) and other emerging viruses remain incompletely defined. A screen of 200,000 compounds for inhibition of an EBOV minigenome (MG) assay that measures the function of the viral polymerase complex identified as hits several compounds with an amino-tetrahydrocarbazole scaffold. This scaffold was structurally similar to GSK983, a compound previously described as having broad-spectrum antiviral activity due to its impairing de novo pyrimidine biosynthesis through inhibition of dihydroorotate dehydrogenase (DHODH)...
October 2018: Antiviral Research
Daniela Bruni, Adam Dignam, Susan Dunne, Devlin Wall-Coughlan, Aisling McCrudden, Karen O'Connell, Caitriona Lyons, Christopher McGuigan, Niall Tubridy, Marion P Butler
IL-27 is a cytokine exerting pleiotropic immunomodulatory effects on a broad spectrum of immune cells. Optimal IL-27 production downstream of TLR3/4 ligand stimulation relies on autocrine type I IFN signaling, defining a first and second phase in IL-27 production. This work shows that IL-1 receptor-associated kinase 1 (IRAK1) limits TLR3/4- and IFNAR-induced IL-27 production. At the mechanistic level, we identified IRAK1 as a novel regulator of STAT1, IRF1, and IRF9. We found hyperactivation of STAT1 together with increased nuclear levels of IRF1 and IRF9 in IRAK1-deficient murine macrophages compared with control cells following stimulation with LPS and poly(I:C)...
October 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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 29, 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...
November 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...
November 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
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