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https://www.readbyqxmd.com/read/28808968/cgamp-quantification-in-virus-infected-human-monocyte-derived-cells-by-hplc-coupled-tandem-mass-spectrometry
#1
Jennifer Paijo, Volkhard Kaever, Ulrich Kalinke
Upon virus infection, cells of the innate immune system such as dendritic cells and macrophages can mount type I interferon (IFN-I) responses that restrict viral dissemination. To inform host cells of virus infection, detection of cytosolic DNA is one important mechanism. Inappropriate sensing of endogenous DNA and subsequent induction of IFN-I responses can also cause autoimmunity, highlighting the need to tightly regulate DNA sensing. The cyclic GMP-AMP synthase (cGAS) was recently identified to be the major sensor of cytosolic DNA that triggers IFN-I expression...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808967/purification-of-cyclic-gmp-amp-from-viruses-and-measurement-of-its-activity-in-cell-culture
#2
Alice Mayer, Jonathan Maelfait, Anne Bridgeman, Jan Rehwinkel
Sensing of cytoplasmic DNA by cGAS is essential for the initiation of immune responses against several viruses. cGAS also plays important roles in some autoinflammatory and autoimmune diseases and may be involved in immune responses targeting cancer cells. Once activated, cGAS catalyzes the formation of the di-nucleotide 2'-3'-cyclic GMP-AMP (cGAMP), which propagates a signaling cascade leading to the production of type I interferons (IFNs). Interestingly, cGAMP is incorporated into enveloped viruses and is transferred to newly infected cells by virions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28802127/investigations-on-the-molecular-mode-of-action-of-the-novel-immunostimulator-zelnate-activation-of-the-cgas-sting-pathway-in-mammalian-cells
#3
Thomas Ilg
Bovine respiratory disease (BRD) is usually prevented or treated with vaccines and/or antibiotics. The use of antibiotics is, however, of concern due to the potential promotion of microbial resistance and the occurrence of residues. Recently an alternative aid in the treatment of BRD, the cationic lipid/bacterial plasmid DNA liposome-based immunomodulator ZelNate, has entered the veterinary market. In the present study, we provide data on the molecular mode of action of ZelNate. Despite the presence of numerous non-methylated CpG motifs in its plasmid DNA, ZelNate proved to be inactive on human and mouse toll-like receptor 9 (TLR9) in cell culture, in both recombinant and natural cellular receptor settings...
August 9, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28801534/cgas-is-activated-by-dna-in-a-length-dependent-manner
#4
Stefanie Luecke, Andreas Holleufer, Maria H Christensen, Kasper L Jønsson, Gerardo A Boni, Lambert K Sørensen, Mogens Johannsen, Martin R Jakobsen, Rune Hartmann, Søren R Paludan
Cytosolic DNA stimulates innate immune responses, including type I interferons (IFN), which have antiviral and immunomodulatory activities. Cyclic GMP-AMP synthase (cGAS) recognizes cytoplasmic DNA and signals via STING to induce IFN production. Despite the importance of DNA in innate immunity, the nature of the DNA that stimulates IFN production is not well described. Using low DNA concentrations, we show that dsDNA induces IFN in a length-dependent manner. This is observed over a wide length-span of DNA, ranging from the minimal stimulatory length to several kilobases, and is fully dependent on cGAS irrespective of DNA length...
August 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28801234/dendritic-cells-but-not-macrophages-sense-tumor-mitochondrial-dna-for-cross-priming-through-signal-regulatory-protein-%C3%AE-signaling
#5
Meng Michelle Xu, Yang Pu, Dali Han, Yaoyao Shi, Xuezhi Cao, Hua Liang, Xiang Chen, Xiao-Dong Li, Liufu Deng, Zhijian J Chen, Ralph R Weichselbaum, Yang-Xin Fu
Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion, but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA, increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs...
August 2, 2017: Immunity
https://www.readbyqxmd.com/read/28771599/ester-alkaloids-from-cephalotaxus-interfere-with-the-2-3-cgamp-induced-type-i-interferon-pathway-in-vitro
#6
Gayoung Park, Sun Yeou Kim, Yoon-Jae Song
Dysregulated activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway by self-DNA contributes to interferonopathy and promotes autoimmune diseases. To identify potential suppressors of STING-induced type I interferon (IFN) induction, ethanol extracts of medicinal plants were screened for inhibitory activity against IFN-ß promoter activation. Notably, 70% ethanol extract of Cephalotaxus koreana specifically down-regulated STING-induced, but not TBK1- or IRF3-induced, IFN-ß promoter activity...
2017: PloS One
https://www.readbyqxmd.com/read/28771381/psychometric-properties-and-factor-structures-of-the-korean-version-of-children-s-depression-rating-scale-revised
#7
Kyoung-Min Kim, Sojeong Nam, Jae-Won Choi, A-Hyun Jung, Soon-Beom Hong, Jun Won Kim, Soo Yeon Kim, Eunji Kim, Jae-Won Kim
OBJECTIVE: The Children's Depression Rating Scale-Revised (CDRS-R) is a valid instrument for the assessment of depressive symptoms in youth, but this measure is yet to be validated in Korea. Thus, the present study aimed to evaluate the validity of the Korean version of the CDRS-R and to determine its factor structures. METHODS: This study included 66 youths between 12 and 17 years of age who participated as part of an ongoing study investigating biomarkers of the antidepressant response and suicidal events in depressed youth...
August 3, 2017: Journal of Child and Adolescent Psychopharmacology
https://www.readbyqxmd.com/read/28765216/key-role-of-the-scavenger-receptor-marco-in-mediating-adenovirus-infection-and-subsequent-innate-responses-of-macrophages
#8
Mareike D Maler, Peter J Nielsen, Nicole Stichling, Idan Cohen, Zsolt Ruzsics, Connor Wood, Peggy Engelhard, Maarit Suomalainen, Ildiko Gyory, Michael Huber, Joachim Müller-Quernheim, Wolfgang W A Schamel, Siamon Gordon, Thilo Jakob, Stefan F Martin, Willi Jahnen-Dechent, Urs F Greber, Marina A Freudenberg, György Fejer
The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages...
August 1, 2017: MBio
https://www.readbyqxmd.com/read/28763795/intratumoral-delivery-of-inactivated-modified-vaccinia-virus-ankara-imva-induces-systemic-antitumor-immunity-via-sting-and-batf3-dependent-dendritic-cells
#9
Peihong Dai, Weiyi Wang, Ning Yang, Cristian Serna-Tamayo, Jacob M Ricca, Dmitriy Zamarin, Stewart Shuman, Taha Merghoub, Jedd D Wolchok, Liang Deng
Advanced cancers remain a therapeutic challenge despite recent progress in targeted therapy and immunotherapy. Novel approaches are needed to alter the tumor immunosuppressive microenvironment and to facilitate the recognition of tumor antigens that leads to antitumor immunity. Poxviruses, such as modified vaccinia virus Ankara (MVA), have potential as immunotherapeutic agents. We show that infection of conventional dendritic cells (DCs) with heat- or ultraviolet-inactivated MVA leads to higher levels of interferon induction than MVA alone through the cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase)-STING cytosolic DNA-sensing pathway...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28759889/mitotic-progression-following-dna-damage-enables-pattern-recognition-within-micronuclei
#10
Shane M Harding, Joseph L Benci, Jerome Irianto, Dennis E Discher, Andy J Minn, Roger A Greenberg
Inflammatory gene expression following genotoxic cancer therapy is well documented, yet the events underlying its induction remain poorly understood. Inflammatory cytokines modify the tumour microenvironment by recruiting immune cells and are critical for both local and systemic (abscopal) tumour responses to radiotherapy. A poorly understood feature of these responses is the delayed onset (days), in contrast to the acute DNA-damage responses that occur in minutes to hours. Such dichotomous kinetics implicate additional rate-limiting steps that are essential for DNA-damage-induced inflammation...
July 31, 2017: Nature
https://www.readbyqxmd.com/read/28759028/innate-immune-sensing-of-cytosolic-chromatin-fragments-through-cgas-promotes-senescence
#11
Selene Glück, Baptiste Guey, Muhammet Fatih Gulen, Katharina Wolter, Tae-Won Kang, Niklas Arndt Schmacke, Anne Bridgeman, Jan Rehwinkel, Lars Zender, Andrea Ablasser
Cellular senescence is triggered by various distinct stresses and characterized by a permanent cell cycle arrest. Senescent cells secrete a variety of inflammatory factors, collectively referred to as the senescence-associated secretory phenotype (SASP). The mechanism(s) underlying the regulation of the SASP remains incompletely understood. Here we define a role for innate DNA sensing in the regulation of senescence and the SASP. We find that cyclic GMP-AMP synthase (cGAS) recognizes cytosolic chromatin fragments in senescent cells...
July 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28744851/post-translational-regulation-of-antiviral-innate-signaling
#12
REVIEW
Yilong Zhou, Chenxi He, Wang Lin, Baoxue Ge
The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required...
July 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28740500/dna-methylation-influences-chlorogenic-acid-biosynthesis-in-lonicera-japonica-by-mediating-ljbzip8-to-regulate-phenylalanine-ammonia-lyase-2-expression
#13
Liangping Zha, Shuang Liu, Juan Liu, Chao Jiang, Shulin Yu, Yuan Yuan, Jian Yang, Yaolong Wang, Luqi Huang
The content of active compounds differ in buds and flowers of Lonicera japonica (FLJ) and L. japonica var. chinensis (rFLJ). Chlorogenic acid (CGAs) were major active compounds of L. japonica and regarded as measurements for quality evaluation. However, little is known concerning the formation of active compounds at the molecular level. We quantified the major CGAs in FLJ and rFLJ, and found the concentrations of CGAs were higher in the buds of rFLJ than those of FLJ. Further analysis of CpG methylation of CGAs biosynthesis genes showed differences between FLJ and rFLJ in the 5'-UTR of phenylalanine ammonia-lyase 2 (PAL2)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28738408/cgas-surveillance-of-micronuclei-links-genome-instability-to-innate-immunity
#14
Karen J Mackenzie, Paula Carroll, Carol-Anne Martin, Olga Murina, Adeline Fluteau, Daniel J Simpson, Nelly Olova, Hannah Sutcliffe, Jacqueline K Rainger, Andrea Leitch, Ruby T Osborn, Ann P Wheeler, Marcin Nowotny, Nick Gilbert, Tamir Chandra, Martin A M Reijns, Andrew P Jackson
DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. Such micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by its own nuclear membrane...
July 24, 2017: Nature
https://www.readbyqxmd.com/read/28738329/distinct-involvement-of-the-sonic-hedgehog-signaling-pathway-in-gastric-adenocarcinoma-of-fundic-gland-type-and-conventional-gastric-adenocarcinoma
#15
Yuzuru Tajima, Takashi Murakami, Tsuyoshi Saito, Takafumi Hiromoto, Yoichi Akazawa, Noriko Sasahara, Hiroyuki Mitomi, Takashi Yao, Sumio Watanabe
BACKGROUND/AIMS: Gastric adenocarcinoma of fundic gland type (GAFG), which is a rare variant of gastric cancer, is reportedly associated with both Wnt/β-catenin signaling activation and guanine nucleotide binding protein, alpha stimulating complex (GNAS) mutations. This study aimed to elucidate potential roles of the Sonic hedgehog (Shh) signaling pathway in GAFG. METHODS: We performed immunostaining for β-catenin and Shh signal-associated proteins, including Patched (Ptch), Smoothened (Smo), and Glioma-associated oncogene-1 (Gli1), and the direct sequencing of GNAS/BRAF/KRAS in 27 GAFGs, and compared them with 30 conventional gastric adenocarcinomas (CGAs)...
July 22, 2017: Digestion
https://www.readbyqxmd.com/read/28733470/dendritic-cell-targeted-lentiviral-vector-immunization-uses-pseudotransduction-and-dna-mediated-sting-and-cgas-activation
#16
Jocelyn T Kim, Yarong Liu, Rajan P Kulkarni, Kevin K Lee, Bingbing Dai, Geoffrey Lovely, Yong Ouyang, Pin Wang, Lili Yang, David Baltimore
Dendritic cell (DC) activation and antigen presentation are critical for efficient priming of T cell responses. Here, we study how lentiviral vectors (LVs) deliver antigen and activate DCs to generate T cell immunization in vivo. We report that antigenic proteins delivered in vector particles via pseudotransduction were sufficient to stimulate an antigen-specific immune response. The delivery of the viral genome encoding the antigen increased the magnitude of this response in vivo but was irrelevant in vitro...
July 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28728796/-lifetime-psychiatric-disorders-a-comparision-study-between-offspring-of-parents-with-bipolar-disorder-type-i-versus-the-offspring-of-community-controls-parents
#17
Juan David Palacio-Ortiz, Cristian Esteban Peña-Quintero, María Alejandra Gómez-Valero, Paula Andrea Bustamante-Gómez, Pilar Helena Arroyave-Sierra, Cristian David Vargas-Upeguí, Carlos López-Jaramillo
INTRODUCTION: Literature reports show that Bipolar Offspring (BO) present with a wide range of psychiatric disorders. Comparison between BO and Control Parent Offspring (CPO) may help to identify which psychopathological findings are specific to this high-risk group. OBJECTIVE: To compare the psychopathological characteristics between a group of BO type-I and a group of CPO, by identifying the presence of psychiatric disorders according the DSM-IV-TR. METHODS: A descriptive-correlational, cross-sectional and comparative study was conducted with 127 offspring of parents with bipolar disorder type-I from the multimodal intervention program (PRISMA) and with 150 CPO between 6 and 30 years of age...
July 2017: Revista Colombiana de Psiquiatría
https://www.readbyqxmd.com/read/28719146/natural-compounds-in-cancer-prevention-effects-of-coffee-extracts-and-their-main-polyphenolic-component-5-cqa-on-oncogenic-ras-proteins
#18
Alessandro Palmioli, Carlotta Cairamelli, Renata Tisi, Michela Spinelli, Gaia De Sanctis, Elena Sacco, Cristina Airoldi
Recent epidemiological studies demonstrate that consumption of healthy foods, especially rich in polyphenols content, might reduce the incidence of cancer and degenerative diseases. In particular, chlorogenic acids (CGAs) occur ubiquitously in food, representing the most abundant polyphenols in the human diet. A number of CGA beneficial biological effects, including anti-inflammatory activity, anti-carcinogenic activity and protection against neurodegenerative diseases have been reported. However, the molecular mechanisms at the basis of these biological activities have not yet been investigated in depth...
July 18, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#19
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28712728/hexim1-and-neat1-long-non-coding-rna-form-a-multi-subunit-complex-that-regulates-dna-mediated-innate-immune-response
#20
Mehdi Morchikh, Alexandra Cribier, Raoul Raffel, Sonia Amraoui, Julien Cau, Dany Severac, Emeric Dubois, Olivier Schwartz, Yamina Bennasser, Monsef Benkirane
The DNA-mediated innate immune response underpins anti-microbial defenses and certain autoimmune diseases. Here we used immunoprecipitation, mass spectrometry, and RNA sequencing to identify a ribonuclear complex built around HEXIM1 and the long non-coding RNA NEAT1 that we dubbed the HEXIM1-DNA-PK-paraspeckle components-ribonucleoprotein complex (HDP-RNP). The HDP-RNP contains DNA-PK subunits (DNAPKc, Ku70, and Ku80) and paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATRIN3). We show that binding of HEXIM1 to NEAT1 is required for its assembly...
August 3, 2017: Molecular Cell
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