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Epigenetics immune response

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https://www.readbyqxmd.com/read/27913794/tlr-ligands-but-not-modulators-of-histone-modifiers-can-induce-the-complex-immune-response-pattern-of-endotoxin-tolerance-in-mammary-epithelial-cells
#1
Juliane Günther, Wolfram Petzl, Holm Zerbe, Hans-Joachim Schuberth, Hans-Martin Seyfert
Excessive stimulation of the TLR4 axis through LPS reduces the expression of some cytokine genes in immune cells, while stimulating the expression of immune defense genes during a subsequent bacterial infection. This endotoxin tolerance (ET) is mediated via epigenetic mechanisms. Priming the udder of cows with LPS was shown to induce ET in mammary epithelial cells (MEC), thereby protecting the udder against reinfection for some time. Seeking alternatives to LPS priming we tried to elicit ET by priming MEC with either lipopeptide (Pam2CSK4) via the TLR2/6 axis or inhibitors of histone-modifying enzymes...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27912316/th2-cells-in-health-and-disease
#2
Toshinori Nakayama, Kiyoshi Hirahara, Atsushi Onodera, Yusuke Endo, Hiroyuki Hosokawa, Kenta Shinoda, Damon J Tumes, Yoshitaka Okamoto
Helper T (Th) cell subsets direct immune responses by producing signature cytokines. Th2 cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth infection and are central to the pathogenesis of many allergic inflammatory diseases. Molecular analysis of Th2 cell differentiation and maintenance of function has led to recent discoveries that have refined our understanding of Th2 cell biology. Epigenetic regulation of Gata3 expression by chromatin remodeling complexes such as Polycomb and Trithorax is crucial for maintaining Th2 cell identity...
November 28, 2016: Annual Review of Immunology
https://www.readbyqxmd.com/read/27903713/-trained-immunity-consequences-for-lymphoid-malignancies
#3
REVIEW
Wendy B C Stevens, Mihai G Netea, Arnon P Kater, Walter J F M van der Velden
In hematological malignancies complex interactions exist between the immune system, microorganisms and malignant cells. On one hand, microorganisms can induce cancer, as illustrated by specific infection-induced lymphoproliferative diseases such as Helicobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. On the other hand, malignant cells create an immunosuppressive environment for their own benefit, but this also results in an increased risk of infections. Disrupted innate immunity contributes to the neoplastic transformation of blood cells by several mechanisms, including the uncontrolled clearance of microbial and autoantigens resulting in chronic immune stimulation and proliferation, chronic inflammation, and defective immune surveillance and anti-cancer immunity...
December 2016: Haematologica
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#4
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27888289/epigenetic-synergism-between-interleukin-4-and-aryl-hydrocarbon-receptor-in-human-macrophages
#5
Wei-Ting Liao, Jian-He Lu, Wei-Ting Wang, Chih-Hsing Hung, Chau-Chyun Sheu, Shau-Ku Huang
: The aryl hydrocarbon receptor (AhR)-ligand axis is involved in immune regulation, but its molecular basis remains to be fully elucidated. Chemokine (C-C motif) ligand 1 (CCL1) is an important chemoattractant, but how CCL1 is regulated remains to be defined. The role of AhR in regulating CCL1 expression in two major subsets of macrophage was investigated. We used a human THP-1 cell line, monocytes, and mouse peritoneal macrophages to generate M(IFN-γ/LPS) and M(IL-4) subsets, and the AhR's ligand effect was determined by the use of a combination of chromatin immunoprecipitation, PCR, and ELISA...
November 25, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27887656/looking-beyond-the-cancer-cell-for-effective-drug-combinations
#6
Jonathan R Dry, Mi Yang, Julio Saez-Rodriguez
Combinations of therapies are being actively pursued to expand therapeutic options and deal with cancer's pervasive resistance to treatment. Research efforts to discover effective combination treatments have focused on drugs targeting intracellular processes of the cancer cells and in particular on small molecules that target aberrant kinases. Accordingly, most of the computational methods used to study, predict, and develop drug combinations concentrate on these modes of action and signaling processes within the cancer cell...
November 25, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27885845/dna-methylation-in-systemic-lupus-erythematosus
#7
Christian M Hedrich, Katrin Mäbert, Thomas Rauen, George C Tsokos
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease facilitated by aberrant immune responses directed against cells and tissues, resulting in inflammation and organ damage. In the majority of patients, genetic predisposition is accompanied by additional factors conferring disease expression. While the exact molecular mechanisms remain elusive, epigenetic alterations in immune cells have been demonstrated to play a key role in disease pathogenesis through the dysregulation of gene expression...
November 25, 2016: Epigenomics
https://www.readbyqxmd.com/read/27879258/nucleophosmin-anaplastic-lymphoma-kinase-npm-alk-the-ultimate-oncogene-and-therapeutic-target
#8
Michael T Werner, Chen Zhao, Qian Zhang, Mariusz A Wasik
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase physiologically expressed by fetal neural cells. However, aberrantly expressed ALK is involved in the pathogenesis of diverse malignancies including distinct types of lymphoma, lung carcinoma, and neuroblastoma. The aberrant ALK expression in non-neural cells results from chromosomal translocations that create novel fusion proteins. These protein hybrids are comprised of the proximal part of a partner gene including its promoter region and the distal part of ALK including coding sequence for the entire kinase domain...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27878451/beyond-genetics-what-causes-type-1-diabetes
#9
REVIEW
Zhen Wang, Zhiguo Xie, Qianjin Lu, Christopher Chang, Zhiguang Zhou
Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated β cell destruction in the pancreas of genetically susceptible individuals. Extensive familial and population genetic studies uncovered the strong linkage and association between HLA gene variants and T1D. Non-HLA genes have also been associated with T1D, such as INS, CTLA4, and PTPN22. T1D is considered as one of the most heritable common diseases. However, evidence that monozygotic twins have incomplete concordance of disease susceptibility provides convincing proof that environmental factors also play important roles in the pathogenesis of the disease...
November 22, 2016: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/27875351/pathogenesis-and-immunotherapy-in-cutaneous-psoriasis-what-can-rheumatologists-learn
#10
Helen Alexander, Frank O Nestle
PURPOSE OF REVIEW: This review presents our current understanding of the pathogenesis and treatment of psoriasis with a particular focus on recent areas of research and emerging concepts. RECENT FINDINGS: Psoriasis arises in genetically predisposed individuals who have an abnormal innate and adaptive immune response to environmental factors. Recent studies have identified novel genetic, epigenetic and immunological factors that play a role in the disease pathogenesis...
January 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27871873/itraq-based-proteomic-analysis-of-defence-responses-triggered-by-the-necrotrophic-pathogen-rhizoctonia-solani-in-cotton
#11
Min Zhang, Shou-Ting Cheng, Hai-Yun Wang, Jia-He Wu, Yuan-Ming Luo, Qian Wang, Fu-Xin Wang, Gui-Xian Xia
: The soil-borne necrotrophic pathogen fungus Rhizoctonia solani is destructive, causing disease in various important crops. To date, little is known about the host defence mechanism in response to invasion of R. solani. Here, an iTRAQ-based proteomic analysis was employed to investigate pathogen-responsive proteins in the disease tolerant/resistant cotton cultivar CRI35. A total of 174 differentially accumulated proteins (DAPs) were identified after inoculation of cotton plants with R...
November 15, 2016: Journal of Proteomics
https://www.readbyqxmd.com/read/27870410/sex-differences-in-neuroinflammation-and-neuroprotection-in-ischemic-stroke
#12
REVIEW
Monica S Spychala, Pedram Honarpisheh, Louise D McCullough
Stroke is not only a leading cause of mortality and morbidity worldwide it also disproportionally affects women. There are currently over 500,000 more women stroke survivors in the US than men, and elderly women bear the brunt of stroke-related disability. Stroke has dropped to the fifth leading cause of death in men, but remains the third in women. This review discusses sex differences in common stroke risk factors, the efficacy of stroke prevention therapies, acute treatment responses, and post-stroke recovery in clinical populations...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27869795/cd68-macrosialin-not-just-a-histochemical-marker
#13
Dimitry A Chistiakov, Murry C Killingsworth, Veronika A Myasoedova, Alexander N Orekhov, Yuri V Bobryshev
CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells...
November 21, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27865897/enigmas-in-tumor-resistance-to-kinase-inhibitors-and-calculation-of-the-drug-resistance-index-for-cancer-dric
#14
REVIEW
C I Edvard Smith
Darwinian selection is also applicable when antibiotics, the immune system or other host factors shape the repertoire of microorganisms, and similarly, clonal selection is the hallmark of tumor evolution. The ongoing revolution in new anti-cancer treatment modalities, combined with an unprecedented precision in characterizing malignant clones at the level below one percent, profoundly improves the understanding of repertoire-tuning mechanisms. There is no fundamental difference between selection of the tumor cells in the presence, or absence, of therapy...
November 16, 2016: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/27865469/interplay-between-inflammation-and-epigenetic-changes-in-cancer
#15
A R Maiuri, H M O'Hagan
Immune responses can suppress tumorigenesis, but also contribute to cancer initiation and progression suggesting a complex interaction between the immune system and cancer. Epigenetic alterations, which are heritable changes in gene expression without changes to the DNA sequence, also play a role in carcinogenesis through silencing expression of tumor suppressor genes and activating oncogenic signaling. Interestingly, epithelial cells at sites of chronic inflammation undergo DNA methylation alterations that are similar to those present in cancer cells, suggesting that inflammation may initiate cancer-specific epigenetic changes in epithelial cells...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/27864925/drug-induced-pyoderma-gangrenosum-a-model-to-understand-the-pathogenesis-of-pyoderma-gangrenosum
#16
REVIEW
B C Wu, E D Patel, A G Ortega-Loayza
Pyoderma gangrenosum (PG) is a rare auto-inflammatory condition in which the alteration of neutrophil function and the innate immune response play key roles in its pathogenesis. Cases of PG have been reported in patients being treated with certain medications, which may help us to understand some of the possible pathways involved in the etiology of PG. The aim of this review is to review the cases of PG triggered by certain drugs and try to thoroughly understand the pathogenesis of the disease. To accomplish this, a PubMed search was completed using the following words: pyoderma gangrenosum, neutrophilic dermatosis, pathophysiology, drug-induced pyoderma gangrenosum...
November 19, 2016: British Journal of Dermatology
https://www.readbyqxmd.com/read/27863852/the-rag-recombinase-beyond-breaking
#17
Chloé Lescale, Ludovic Deriano
DNA double-strand breaks (DSBs) are commonly seen as lesions that threaten genome integrity and contribute to cancer and aging processes. However, in the context of antigen receptor gene assembly, known as V(D)J recombination, DSBs are obligatory intermediates that allow the establishment of genetic diversity and adaptive immunity. V(D)J recombination is initiated when the lymphoid-restricted recombination-activating genes RAG1 and RAG2 are expressed and form a site-specific endonuclease (the RAG nuclease or RAG recombinase)...
November 15, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27863248/%C3%AE-glucan-reverses-the-epigenetic-state-of-lps-induced-immunological-tolerance
#18
Boris Novakovic, Ehsan Habibi, Shuang-Yin Wang, Rob J W Arts, Robab Davar, Wout Megchelenbrink, Bowon Kim, Tatyana Kuznetsova, Matthijs Kox, Jelle Zwaag, Filomena Matarese, Simon J van Heeringen, Eva M Janssen-Megens, Nilofar Sharifi, Cheng Wang, Farid Keramati, Vivien Schoonenberg, Paul Flicek, Laura Clarke, Peter Pickkers, Simon Heath, Ivo Gut, Mihai G Netea, Joost H A Martens, Colin Logie, Hendrik G Stunnenberg
Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic approach to characterize the molecular events involved in LPS-induced tolerance in a time-dependent manner. Mechanistically, LPS-treated monocytes fail to accumulate active histone marks at promoter and enhancers of genes in the lipid metabolism and phagocytic pathways. Transcriptional inactivity in response to a second LPS exposure in tolerized macrophages is accompanied by failure to deposit active histone marks at promoters of tolerized genes...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27862100/role-of-epigenetic-modification-and-immunomodulation-in-a-murine-prostate-cancer-model
#19
Jay E Sulek, Samuel P Robinson, Albert A Petrossian, Shaoqing Zhou, Ekaterine Goliadze, Masoud H Manjili, Amir Toor, Georgi Guruli
INTRODUCTION: Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC)...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27854240/the-impact-of-chemotherapy-radiation-and-epigenetic-modifiers-in-cancer-cell-expression-of-immune-inhibitory-and-stimulatory-molecules-and-anti-tumor-efficacy
#20
REVIEW
Jessica Ann Chacon, Keith Schutsky, Daniel J Powell
Genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers are used for the treatment of cancer due to their apoptotic effects on the aberrant cells. However, these therapies may also induce widespread changes within the immune system and cancer cells, which may enable tumors to avoid immune surveillance and escape from host anti-tumor immunity. Genomic destabilizers can induce immunogenic death of tumor cells, but also induce upregulation of immune inhibitory ligands on drug-resistant cells, resulting in tumor progression...
November 14, 2016: Vaccines
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