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DNA methylation immune response

Matthew Gordon Varga, Maria Blanca Piazuelo, Judith Romero-Gallo, Alberto G Delgado, Giovanni Suarez, Morgan E Whitaker, Uma S Krishna, Rachna V Patel, Eric P Skaar, Keith T Wilson, Holly M Scott Algood, Richard M Peek
Helicobacter pylori induces chronic gastritis in humans and infection can persist for decades. One H. pylori strain-specific constituent that augments disease risk is the cag pathogenicity island. The cag island encodes a type IV secretion system (T4SS) that translocates DNA into host cells. Toll-like receptor 9 (TLR9) is an innate immune receptor that detects hypo-methylated CpG DNA motifs. In this study, we sought to define the role of the H. pylori cag T4SS on TLR9-mediated responses in vivo H. pylori strain PMSS1 or its cagE(-) mutant, which fails to assemble a T4SS, were used to infect wild-type or Tlr9(-/-) C57BL/6 mice...
October 6, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Jun Udagawa, Kodai Hino
Epidemiological studies suggest that exposure to prenatal stressors, including malnutrition, maternal immune activation (MIA), and adverse life events, is associated with increased risks of schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD). However, the underlying pathophysiological mechanisms are unclear. The first trimester of pregnancy is particularly a vulnerable period. During this period, the self-renewal of neural stem cells and neurogenesis vigorously occur, and synaptic connections are partially formed in the telencephalon...
2016: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
Amber Dahlin, Scott T Weiss
Aspirin-exacerbated respiratory disease (AERD) severity and its clinical phenotypes are characterized by genetic variation within pathways for arachidonic acid metabolism, inflammation, and immune responses. Epigenetic effects, including DNA methylation and histone protein modification, contribute to regulation of many genes that contribute to inflammatory states in AERD. The development of noninvasive, predictive clinical tests using data from genetic, epigenetic, pharmacogenetic, and biomarker studies will improve precision medicine efforts for AERD and asthma treatment...
November 2016: Immunology and Allergy Clinics of North America
Y H Zhang, J L Meng, Y Gao, J Y Zhang, S L Niu, X Z Yu, Y B Li, Y T Guan, B X Sun, Z H Zhao
DNA methylation is an important epigenetic modification in eukaryotes, which plays a significant role in regulating gene expression. When the host is invaded by the influenza virus, gene expression is regulated via changes in DNA methylation levels or patterns, leading to the activation or suppression of relevant signaling pathways or networks, triggering a series of immune responses against viral invasion. Here, we investigated the changes in genomic DNA methylation in the immune organs of chicken infected with H5N1 influenza virus...
September 16, 2016: Genetics and Molecular Research: GMR
Melanie R Hassler, Walter Pulverer, Ranjani Lakshminarasimhan, Elisa Redl, Julia Hacker, Gavin D Garland, Olaf Merkel, Ana-Iris Schiefer, Ingrid Simonitsch-Klupp, Lukas Kenner, Daniel J Weisenberger, Andreas Weinhaeusel, Suzanne D Turner, Gerda Egger
Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+) and NPM-ALK-negative (ALK-) anaplastic large-cell lymphoma (ALCL). We find that ALK+ and ALK- ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters...
October 4, 2016: Cell Reports
David L Marks, Rachel Lo Olson, Martin E Fernandez-Zapico
Stromal cells of the tumor microenvironment have been shown to play important roles in both supporting and limiting cancer growth. The altered phenotype of tumor-associated stromal cells (fibroblasts, immune cells, endothelial cells etc.) is proposed to be mainly due to epigenetic dysregulation of gene expression; however, only limited studies have probed the roles of epigenetic mechanisms in the regulation of stromal cell function. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation and histone post-translational modification-based gene expression regulation, and miRNA-mediated translational regulation) drive aspects of stromal cell phenotype, and discuss the implications of these findings for treatment of malignancies...
October 4, 2016: Epigenomics
Ye Shu, Qinghua Hu, Hai Long, Christopher Chang, Qianjin Lu, Rong Xiao
Autoimmune diseases are characterized by aberrant immune responses against healthy cells and tissues. However, the exact mechanisms underlying the development of these conditions remain unknown. CD4+CD25+ regulatory T cells (Tregs) are a subset of mature T cells which have an important role in maintaining immune homeostasis and preventing autoimmune diseases. Forkhead box p3 (Foxp3), a member of the fork head transcription factor family, is recognized as a marker of CD4+CD25+ Tregs. The decreased number and/or function of CD4+CD25+ Tregs in peripheral blood and related tissues has been demonstrated in systemic lupus erythematosus, systemic sclerosis, and other autoimmune diseases, which are at least partially regulated by epigenetic mechanisms...
September 29, 2016: Clinical Reviews in Allergy & Immunology
Ferenc Sipos, Gábor Firneisz, Györgyi Műzes
Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation...
September 21, 2016: World Journal of Gastroenterology: WJG
Maciej Tarnowski, Michał Czerewaty, Anna Deskur, Krzysztof Safranow, Wojciech Marlicz, Elżbieta Urasińska, Mariusz Z Ratajczak, Teresa Starzyńska
Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study...
2016: Disease Markers
Zhen Cao, Shihua Zhang
To investigate the commonalities and specificities across tumor lineages, we perform a systematic pan-cancer transcriptomic study across 6744 specimens. We find six pan-cancer subnetwork signatures which relate to cell cycle, immune response, Sp1 regulation, collagen, muscle system and angiogenesis. Moreover, four pan-cancer subnetwork signatures demonstrate strong prognostic potential. We also characterize 16 cancer type-specific subnetwork signatures which show diverse implications to somatic mutations, somatic copy number aberrations, DNA methylation alterations and clinical outcomes...
2016: Scientific Reports
Valeria Lucarini, Carla Buccione, Giovanna Ziccheddu, Francesca Peschiaroli, Paola Sestili, Rossella Puglisi, Gianfranco Mattia, Cristiana Zanetti, Isabella Parolini, Laura Bracci, Iole Macchia, Alessandra Rossi, Maria Teresa D'Urso, Daniele Macchia, Massimo Spada, Adele De Ninno, Annamaria Gerardino, Pamela Mozetic, Marcella Trombetta, Alberto Rainer, Luca Businaro, Giovanna Schiavoni, Fabrizio Mattei
Resistance to Type I IFN (IFN-I)-induced anti-neoplastic effects has been reported in many tumors and arise, in part, from epigenetic silencing of IFN-stimulated genes by DNA methylation. We hypothesized that restoration of IFN-stimulated genes by co-administration of the demethylating drug 5-Aza-2'-Deoxycitidine (Decitabine; DAC) may enhance the susceptibility to IFN-I-mediated anti-tumoral effects in melanoma. We show that combined administration of IFN-I and DAC significantly inhibits the growth of murine and human melanoma cells, both in vitro and in vivo...
September 10, 2016: Journal of Investigative Dermatology
Lemeng Zhang, Songyun Deng, Shuangping Zhao, Yuhang Ai, Lina Zhang, Pinhua Pan, Xiaoli Su, Hongyi Tan, Dongdong Wu
The pathogenesis of sepsis is complex. Mitochondrial dysfunction, which is responsible for energy metabolism, intrinsic apoptotic pathway, oxidative stress, and systemic inflammatory responses, is closely related with severe sepsis induced death. Mitochondria DNA (mtDNA) contain un-methylated cytosine phosphate guanine (CpG) motifs, which exhibit immune stimulatory capacities. The aim of this study was to investigate the role and mechanism of mtDNA release on lipopolysaccharide (LPS) induced acute lung injury (ALI) and systemic inflammation...
2016: International Journal of Molecular Sciences
Tianxiao Huan, Roby Joehanes, Claudia Schurmann, Katharina Schramm, Luke C Pilling, Marjolein J Peters, Reedik Mägi, Dawn DeMeo, George T O'Connor, Luigi Ferrucci, Alexander Teumer, Georg Homuth, Reiner Biffar, Uwe Völker, Christian Herder, Melanie Waldenberger, Annette Peters, Sonja Zeilinger, Andres Metspalu, Albert Hofman, André G Uitterlinden, Dena G Hernandez, Andrew B Singleton, Stefania Bandinelli, Peter J Munson, Honghuang Lin, Emelia J Benjamin, Tõnu Esko, Hans J Grabe, Holger Prokisch, Joyce B J van Meurs, David Melzer, Daniel Levy
Cigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a meta-analysis of transcriptome-wide gene expression using whole blood-derived RNA from 10,233 participants of European ancestry in six cohorts (including 1421 current and 3955 former smokers) to identify associations between smoking and altered gene expression levels. At a false discovery rate (FDR) <0...
August 29, 2016: Human Molecular Genetics
Layale Yaghi, Isabelle Poras, Renata T Simoes, Eduardo A Donadi, Jörg Tost, Antoine Daunay, Bibiana Sgorla de Almeida, Edgardo D Carosella, Philippe Moreau
HLA-G is an immune checkpoint molecule with specific relevance in cancer immunotherapy. It was first identified in cytotrophoblasts, protecting the fetus from maternal rejection. HLA-G tissue expression is very restricted but induced in numerous malignant tumors such as glioblastoma, contributing to their immune escape. Hypoxia occurs during placenta and tumor development and was shown to activate HLA-G. We aimed to elucidate the mechanisms of HLA-G activation under conditions combining hypoxia-mimicking treatment and 5-aza-2'deoxycytidine, a DNA demethylating agent used in anti-cancer therapy which also induces HLA-G...
August 26, 2016: Oncotarget
Nino A Espinas, Hidetoshi Saze, Yusuke Saijo
Immune recognition of pathogen-associated molecular patterns or effectors leads to defense activation at the pathogen challenged sites. This is followed by systemic defense activation at distant non-challenged sites, termed systemic acquired resistance (SAR). These inducible defenses are accompanied by extensive transcriptional reprogramming of defense-related genes. SAR is associated with priming, in which a subset of these genes is kept at a poised state to facilitate subsequent transcriptional regulation...
2016: Frontiers in Plant Science
Ana Carolina Morandini, Carlos F Santos, Ӧzlem Yilmaz
Epigenetic mechanisms have rapidly and controversially emerged as silent modulators of host defenses that can lead to a more prominent immune response and shape the course of inflammation in host. Thus, the epigenetics can both drive the production of specific inflammatory mediators and control the magnitude of host response. The epigenetic actions that are predominantly shown to modulate the host defense against microbial pathogens are DNA methylation, histone modification, and the activity of non-coding RNAs...
August 18, 2016: Pathogens and Disease
Gourisankar Ghosh, Malini Sen
Regulatory roles of protein and DNA modifications in gene expression during host defense have long been appreciated. In a recent article published in Nature Immunology, Li et al. (2016) provide a unique glimpse of yet another aspect of coordinated DNA methylation and protein acetylation in host response to pathogenic stimuli. They elegantly demonstrate that DNA methylation and transcriptional activation at the HDAC9 promoter by DNMT3a, along with lysine deacetylation of TBK1 by HDAC9, are essential events during host defense...
August 18, 2016: Molecular Cell
Sahar Houshdaran, Camran R Nezhat, Kim Chi Vo, Zara Zelenko, Juan C Irwin, Linda C Giudice
Endometriosis is an estrogen-dependent, progesterone-resistant disorder largely derived from retrograde transplantation of menstrual tissue/cells into the pelvis, eliciting an inflammatory response, pelvic pain and infertility. Eutopic endometrium (within the uterus), giving rise to pelvic disease, displays cycle-dependent transcriptomic, proteomic, and signaling abnormalities, and while its DNA methylation profiles dynamically change across the cycle in healthy women, studies in endometriosis are limited. Herein, we investigated the DNA methylome and associated gene expression in three phases of the cycle in eutopic endometrium of women with severe endometriosis versus controls, matched for ethnicity, medications, smoking, and no recent contraceptive steroid use...
August 17, 2016: Biology of Reproduction
Sung-Chou Li, Wen-Ching Chan, Ying-Hsien Huang, Mindy Ming-Huey Guo, Hong-Ren Yu, Fu-Chen Huang, Hsing-Chun Kuo, Ho-Chang Kuo
BACKGROUND: Kawasaki disease (KD) is an autoimmune disease preferentially attacking children younger than five years worldwide. So far, the principal treatment to KD is the administration of Intravenous immunoglobulin (IVIG). Although DNA methylation plays important regulation roles in diseases, few studies investigated the regulation roles of DNA methylation in KD. METHODS: In this study, we focused not only on the DNA methylation alterations resulted from KD onset but also on DNA methylation alterations resulted from IVIG administration...
2016: BMC Medical Genomics
Bingshe Han, Wenhao Li, Zuozhou Chen, Qiongqiong Xu, Juntao Luo, Yingdi Shi, Xiaoxia Li, Xiaonan Yan, Junfang Zhang
DNA methylation is an essential epigenetic mechanism involved in multiple biological processes. However, the relationship between DNA methylation and cold acclimation remains poorly understood. In this study, Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) was performed to reveal a genome-wide methylation profile of zebrafish (Danio rerio) embryonic fibroblast cells (ZF4) and its variation under cold pressure. MeDIP-seq assay was conducted with ZF4 cells cultured at appropriate temperature of 28°C and at low temperature of 18°C for 5 (short-term) and 30 (long-term) days, respectively...
2016: PloS One
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