scholarly journals Major surgery induces acute changes in measured DNA methylation associated with immune response pathways

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryoichi Sadahiro ◽  
Bridget Knight ◽  
Ffion James ◽  
Eilis Hannon ◽  
John Charity ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Major Surgery ◽  
Acute Changes

scholarly journals Major surgery induces acute changes in DNA methylation associated with activation of the immune response

2019 ◽  
Author(s):  
Ryoichi Sadahiro ◽  
Bridget Knight ◽  
Ffion James ◽  
Eilis Hannon ◽  
John Charity ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune System ◽  
Mononuclear Cells ◽  
Regulation Of Gene Expression ◽  
Invasive Procedure ◽  
Serum Levels ◽  
Major Surgery ◽  
Peripheral Blood Mononuclear ◽  
Acute Changes ◽  
Discharge From Hospital

AbstractBackgroundSurgery is an invasive procedure evoking acute inflammatory and immune responses that are believed to mediate risk for postoperative complications including cognitive dysfunction and delirium. Although the specific mechanisms driving these responses have not been well-characterized, they are hypothesized to involve the epigenetic regulation of gene expression. We quantified genome-wide levels of DNA methylation in purified peripheral blood mononuclear cells (PBMCs) longitudinally collected from 55 elderly patients undergoing three types of major surgery (elective colorectal and hip replacement surgery, and emergency hip fracture surgery), comparing samples collected at baseline to those collected immediately post-operatively and at discharge from hospital.ResultsMajor surgery was associated with acute changes in DNA methylation at sites annotated to immune system genes, paralleling changes in serum-levels of markers including C-reactive protein (CRP) and Interleukin 6 (IL-6) measured in the same individuals. Although many of the observed changes in DNA methylation are consistent across the three types of surgery, there is notable heterogeneity between surgery types at certain loci. The acute changes in DNA methylation induced by surgery are relatively stable in the postoperative period, generally persisting until discharge from hospital.ConclusionsOur results highlight the dramatic alterations in gene regulation induced by invasive surgery, primarily reflecting upregulation of the immune system in response to trauma, wound healing and anaesthesia.

PS02.176: LINE-1 METHYLATION LEVEL AND LOCAL IMMUNE RESPONSE IN ESOPHAGEAL CANCER

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 172-172
Author(s):  
Yoshifumi Baba ◽  
Taisuke Yagi ◽  
Yuki Kiyozumi ◽  
Yukiharu Hiyoshi ◽  
Masaaki Iwatsuki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Esophageal Cancer ◽  
Methylation Level ◽  
Cpg Island ◽  
Surrogate Marker ◽  
Esophageal Tumor ◽  
Local Immune Response ◽  
Dna Hypomethylation ◽  
Response Status

Abstract Background In cancer cells, DNA methylation may be altered in two principle ways; global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Since Long interspersed element-1 (LINE-1 or L1; a repetitive DNA retrotransposon) constitutes a substantial portion (approximately 17%) of the human genome, the extent of LINE-1 methylation is regarded as a surrogate marker of global DNA methylation. In previous studies, we demonstrated that LINE-1 hypomethylation was strongly associated with a poor prognosis in esophageal cancer, supporting its potential role as a prognostic marker (Ann Surg 2012). We also found that LINE-1-hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6 (Clin Cancer Res 2014). Given that immunotherapy, as represented by PD-1/PD-L1-targeting antibodies, has increasingly gained attention as a novel treatment strategy for esophageal cancer, better understanding of local immune response status in esophageal cancer is important. The aim of this study is to evaluate the relationship between LINE-1 methylation level and local immune response in esophageal cancer. Methods Using a non-biased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (CD8 expression) by immunohistochemical analysis (Ann Surg 2017). Results TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001). TIL-negative cases demonstrated significantly lower LINE-1 methylation level compared with TIL-positive cases (P = 0.012). This finding certainly supports that LINE-1 methylation level may influence the local immune response status. Conclusion PD-L1 expression was not related with LINE-1 methylation level. Further investigations in this field would provide deeper insights into esophageal tumor immunology and assist the development of new therapeutic strategies against esophageal cancer. Disclosure All authors have declared no conflicts of interest.

scholarly journals Whole-Blood Methylation Analysis Reveals Respiratory Environmental Functional Pathways Involved in Severity Following SARS-CoV-2 Infection

2021 ◽  
Author(s):  
Guillermo Barturen ◽  
Elena Carnero-Montoro ◽  
Manuel Martínez-Bueno ◽  
Silvia Rojo-Rello ◽  
Beatriz Sobrino ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Epigenetic Regulation ◽  
Strong Relationship ◽  
Autoimmune Disorder ◽  
Methylation Analysis ◽  
Functional Pathways ◽  
Interferon Responses ◽  
Inflammatory Syndrome ◽  
Dna Genotyping

SARS-CoV-2 causes a severe inflammatory syndrome called COVID-19 that primarily affects the lungs leading, in many cases, to bilateral pneumonia, severe dyspnea and in ~5% of the cases, death. The mechanisms through which this occurs are still being elucidated. A strong relationship between COVID-19 progression and autoimmune disorder pathogenesis has been identified as an exacerbated interferon immune response or an inflammatory condition mediated by an increase of pro-inflammatory cytokine production, among other. DNA methylation is known to regulate immune response processes, thus COVID-19 progression might be also conditioned by DNA methylation changes not studied in depth, yet. Thus, here an epigenome-wide DNA methylation analysis combined with DNA genotyping for 101 and 473 SARS-CoV-2 negative and positive lab tested individuals, respectively, from two different clinical centers is presented in order to evaluate the implications of the epigenetic regulation in the course of COVID-19 disease. The results reveal the existence of an epigenome regulation of functional pathways associated with the COVID-19 progression, such as innate interferon responses, hyperactivation of B and T lymphocytes, phagocytosis and innate C-type lectin DC-SIGN. These DNA methylation changes were found to be regulated by genetic loci associated with COVID-19 susceptibility and autoimmune disease. In mild COVID-19 patients hypomethylation of CpGs regulating genes within the AKT signaling pathway, and the hypermethylation of a group of CpGs related to environmental traits regulating IL-6 expression via the transcription factor CEBP, discriminate these individuals from those who develop the most critical outcomes of the disease. Thus, the analysis points out to an environmental contribution that mediated by DNA methylation changes in SARS-CoV-2 positive patients, might be playing a role in triggering the cytokine storm described in the most severe cases. In addition, important differences were found in terms of epigenetic regulation between severe and mild cases when compared with systemic autoimmune diseases.

scholarly journals DNA Methylation Patterns of Interferon Gamma Gene Promoter and Serum Level in Pulmonary Tuberculosis: Their Role in Prognosis

2019 ◽  
Vol 16 (1) ◽  
pp. 0178
Author(s):  
Zayr Et al.
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Interferon Gamma ◽  
Gene Promoter ◽  
Innate Immune ◽  
Healthy Controls ◽  
Healthy Control ◽  
Ifn Γ ◽  
Methylation Patterns ◽  
Normal Controls

Tuberculosis (TB) still remains an important medical problem due to high levels of morbidity and mortality worldwide. A series of innate immune mechanisms that create a cytokine network control the pathogenesis of tuberculosis and this response has the capacity to modify the host genomic DNA structure through epigenetic mechanisms such as DNA methylation which could constantly alter the local gene expression pattern that can modulate the metabolism of the tissues and the immune-response. Interferon-gamma (IFN-γ) is an important pro-inflammatory cytokine regulator of the innate immune response to TB. This study aims to determine DNA methylation patterns of INF-γ gene promoter and measure serum IFN- γ level in newly diagnosed TB patients, relapse TB patients, and healthy control, in order to study the possibility of using these as a biomarker for the prognosis of TB stages in patients. The current case-control study included 66 patients with TB and 33 healthy control subjects. DNA was extracted from peripheral blood(PB) of included subjects and modified using sodium bisulfate specific kit. DNA methylation patterns of IFN-γ gene promoter was determine by using methylation specific polymerase chain reaction(MS-PCR).Serum IFN-γ level  was determined using enzyme linked immune-sorbent assay(ELISA). Results showed that percentages of DNA methylation patterns in normal controls, newly diagnostic TB patients and relapse TB patients were (63.3%, 18.2% and 21.2% respectively). Also, higher significant differences (P≤0.0001) of  un-methylated  IFN-γ gene promoter patterns in newly diagnostic TB patients  than  relapse TB patients comparison with healthy controls. The percentage of un-methylated DNA patterns in healthy controls, newly diagnostic TB patients and relapse TB patients were (9.9%, 39.4% and 51.5%, respectively). The mean of serum IFN-γ levels (pg/ml) for normal controls, newly diagnostic TB patients and relapse TB patients were (59.3± 13.8,75.8±24.3 and 69.6±18.7,respectively).In conclusion, there is a relative association between methylation of IFN-γ gene promoter and predisposing to TB progression.

Host defense in malnutrition

PEDIATRICS ◽  
1977 ◽  
Vol 59 (4) ◽  
pp. 490-495
Author(s):  
Michael Katz ◽  
E. Richard Stiehm
Keyword(s):  
Immune Response ◽  
Model Systems ◽  
Major Surgery ◽  
Nutrient Deficiencies ◽  
Industrialized Countries ◽  
Critical Approach ◽  
Value Judgment ◽  
Nutritional Interventions ◽  
A Value ◽  
Important Health

It has not been possible to relate a particular immune failure or deficiency to absence of a specific nutrient. All of these studies have viewed the totality of malnutrition and, yet, it would seem reasonable to expect that specific nutrient deficiencies would affect the response differently and that the almost infinite number of possible interactions among nutrients may have their particular effect. Furthermore, it has not been possible to evaluate any of these studies in terms of the influences that infections themselves have brought to bear. These considerations have led us to conclude that studies of man cannot be carried out with a precision required for the definitive answers. This is not a defeatist notion, but rather a value judgment that prompts us to recommend a more intensive series of investigations in animal model systems, the conclusions of which could then be applied selectively to clinical studies of man. The important question that must be considered is possible nutritional interventions in severely infected patients, such as those undergoing major surgery or immunosuppressive therapy. Potential dangers of using live attenuated viral vaccines in malnourished populations must be evaluated. It is necessary to assess the possibility that such vaccine viruses unchecked by normal immune response in malnourished individuals may lead to the establishment of states of latency and, ultimately, slow infections. The need for further studies has been given recognition by a workshop conference held in May 1975 under the title "Malnutrition and the Immune Response"; the proceedings are soon to be published in book form.57 The question of the influences of infection upon the state of nutrition has also been considered in a recent workshop, the proceedings of which will also be published.58 We believe that the current critical approach to this important health problem will generate answers long wanting. When these answers do become available, they will guide us into better care not only of the malnourished in the developing world, but also of those in the industrialized countries.

scholarly journals Bacterial Lipopolysaccharide Induced Alterations of Genome-Wide DNA Methylation and Promoter Methylation of Lactation-Related Genes in Bovine Mammary Epithelial Cells

Toxins ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 298 ◽  
Author(s):  
Jingbo Chen ◽  
Yongjiang Wu ◽  
Yawang Sun ◽  
Xianwen Dong ◽  
Zili Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Mrna Expression ◽  
Promoter Methylation ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Bovine Mammary Epithelial Cells ◽  
Genome Wide ◽  
Immune Response Pathway ◽  
Gene Mrna

Bacterial lipopolysaccharide (LPS) could result in poor lactation performance in dairy cows. High methylation of DNA is associated with gene repression. However, it is unclear whether LPS could suppress the expression of lactation-related genes by inducing DNA methylation. Therefore, the objective of this study was to investigate the impact of LPS on genome-wide DNA methylation, using methylated DNA immunoprecipitation with high-throughput sequencing (MeDIP-seq) and on the promoter methylation of lactation-related genes using MassArray analysis in bovine mammary epithelial cells. The bovine mammary epithelial cell line MAC-T cells were treated for 48 h with LPS at different doses of 0, 1, 10, 100, and 1000 endotoxin units (EU)/mL (1 EU = 0.1 ng). The results showed that the genomic methylation levels and the number of methylated genes in the genome as well as the promoter methylation levels of milk genes increased when the LPS dose was raised from 0 to 10 EU/mL, but decreased after further increasing the LPS dose. The milk gene mRNA expression levels of the 10 EU/mL LPS treatment were significantly lower than these of untreated cells. The results also showed that the number of hypermethylated genes was greater than that of hypomethylated genes in lipid and amino acid metabolic pathways following 1 and 10 EU/mL LPS treatments as compared with control. By contrast, in the immune response pathway the number of hypomethylated genes increased with increasing LPS doses. The results indicate LPS at lower doses induced hypermethylation of the genome and promoters of lactation-related genes, affecting milk gene mRNA expression. However, LPS at higher doses induced hypomethylation of genes involved in the immune response pathway probably in favor of immune responses.

scholarly journals DNA methylation–based immune response signature improves patient diagnosis in multiple cancers

2017 ◽  
Vol 127 (8) ◽  
pp. 3090-3102 ◽  
Author(s):  
Jana Jeschke ◽  
Martin Bizet ◽  
Christine Desmedt ◽  
Emilie Calonne ◽  
Sarah Dedeurwaerder ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Multiple Cancers ◽  
Patient Diagnosis

scholarly journals Broad DNA methylation changes of spermatogenesis, inflammation and immune response‐related genes in a subgroup of sperm samples for assisted reproduction

Andrology ◽  
2013 ◽  
Vol 1 (6) ◽  
pp. 822-829 ◽  
Author(s):  
B. Schütte ◽  
N. El Hajj ◽  
J. Kuhtz ◽  
I. Nanda ◽  
J. Gromoll ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Assisted Reproduction

scholarly journals Genome-Wide DNA Methylation Variations Between Grass Carp with Different Ages

2020 ◽  
Author(s):  
Libo He ◽  
Denghui Zhu ◽  
Pengfei Chu ◽  
Yongming Li ◽  
Lanjie Liao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Immune Response ◽  
Grass Carp ◽  
Energy Production ◽  
Gene Body ◽  
Global Methylation ◽  
Genome Wide ◽  
Age Dependent ◽  
Different Ages

Abstract Background: Grass carp is an important farmed fish in China that infected by many pathogens, especially grass carp reovirus (GCRV). Notably, grass carp showed age-dependent susceptibility to GCRV, while the mechanism remains unclear. Herein, we performed a genome-wide survey of differences in DNA methylation and gene expression between five months old grass carp (FMO, sensitive to GCRV) and three years old grass carp (TYO, resistant to GCRV) aim to uncover the mechanism.Results: Colorimetric quantification revealed global methylation level of TYO fish was higher than that of FMO fish. Whole-genome bisulfite sequencing (WGBS) of two groups revealed 6,214 differentially methylated regions (DMRs) and 4,052 differentially methylated genes (DMGs), with most of DMRs and DMGs showed hypermethylation patterns in TYO fish. Correlation analysis indicated that DNA hypomethylation in promoter negative correlated with gene expression, whereas positive correlation was found between gene-body DNA hypermethylation and gene expression. Enrichment analysis revealed that promoter hypo-DMGs in TYO fish were significant enriched in pathways involved in immune response while gene-body hyper-DMGs in TYO fish were significant enriched in terms related to RNA transcription, biosynthetic, and energy production. RNA-seq indicated these terms or pathways involved in immune response, biosynthetic, and energy production also significant enriched for the up-regulated genes in TYO fish. Conclusions: Collectively, these results revealed the genome-wide DNA methylation variations between grass carp with different ages. DNA methylation and gene expression variations in genes involved in immune response, biosynthetic, and energy production may contributed to the age-dependent susceptibility to GCRV in grass carp. Our results will provide important information for the disease-resistant breeding programs of grass carp and may also benefit to the research of age-dependent diseases in human.

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