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Epigenetics inflammation

Hee Yeon Won, Eun Sook Hwang
Regulatory T (Treg) cells with high expression of both CD25 and Foxp3 are developed in the thymus and also peripheral tissues. Treg cells suppress the activation and functions of effector T cells raised against specific antigens and are crucial for maintaining immune homeostasis. Treg cell development is associated with the induction of and epigenetic alterations of forkhead transcription factor Foxp3. Foxp3 expression is increased by the activation of several transcription factors including nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT), and Smad3 in response to various signals such as TGFβ, retinoic acid, and rapamycin...
October 25, 2016: Archives of Pharmacal Research
Yanfen Li, Malavika K Adur, Athilakshmi Kannan, Juanmahel Davila, Yuechao Zhao, Romana A Nowak, Milan K Bagchi, Indrani C Bagchi, Quanxi Li
Endometriosis, defined as growth of the endometrial cells outside the uterus, is an inflammatory disorder that is associated with chronic pelvic pain and infertility in women of childbearing age. Although the estrogen-dependence of endometriosis is well known, the role of progesterone in development of this disease remains poorly understood. In this study, we developed a disease model in which endometriosis was induced in the peritoneal cavities of immunocompetent female mice, and maintained with exogenous estrogen...
2016: PloS One
Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
October 17, 2016: Immunobiology
Srimoyee Ghosh, Jose M Lora
Epigenetic control of gene expression is enforced in part through histone modifications. Bromodomain and extra terminal domain (BET) proteins function as crucial chromatin readers, responsible for interpretation of the chromatin code in diverse cellular contexts, ultimately impacting gene transcription. BET proteins can play a major role in inflammation by profoundly affecting the biology of the Thelper 17 (TH17) lineage. We summarize recent studies focusing on BET inhibition as a viable therapeutic alternative for the control of autoimmune diseases driven by aberrant activation of TH17 cells...
March 2016: Drug Discovery Today. Technologies
Katharina Meier, Stefan K Drexler, Franziska C Eberle, Karine Lefort, Amir S Yazdi
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC...
2016: PloS One
Paule V Joseph, Sarah K Abey, Wendy A Henderson
Nutrition is a factor involved in inflammation and a modulator of risk toward some cancers, and the complexity of linkages between dietary components and epigenetics mechanisms (e.g., DNA methylation, histone modification, chromatin remodeling) may affect the inflammation phenotype and the development of cancer. An increasing number of studies support the role of diet in cancer development, prevention, and treatment. Although current knowledge regarding nutri-epigenetics is expanding, more work is needed, and nurse scientists have the potential to significantly contribute to the expansion of this knowledge...
November 1, 2016: Oncology Nursing Forum
David F Tough, Paul P Tak, Alexander Tarakhovsky, Rab K Prinjha
Immune-mediated diseases are clinically heterogeneous but they share genetic and pathogenic mechanisms. These diseases may develop from the interplay of genetic factors and environmental or lifestyle factors. Exposure to such factors, including infectious agents, is associated with coordinated changes in gene transcription owing to epigenetic alterations. A growing understanding of how epigenetic mechanisms control gene expression patterns and cell function has been aided by the development of small-molecule inhibitors that target these processes...
October 21, 2016: Nature Reviews. Drug Discovery
Linda Witek Janusek, Dina Tell, Noni Gaylord-Harden, Herbert L Mathews
African American men (AAM) who are exposed to trauma and adversity during their early life are at greater risk for poor health over their lifespan. Exposure to adversity during critical developmental windows may embed an epigenetic signature that alters expression of genes that regulate stress response systems, including those genes that regulate the inflammatory response to stress. Such an epigenetic signature may increase risk for diseases exacerbated by inflammation, and may contribute to health disparity...
October 17, 2016: Brain, Behavior, and Immunity
Olga Ruiz-Andres, Maria Dolores Sanchez-Niño, Juan Antonio Moreno, Marta Ruiz-Ortega, Adrian Mario Ramos, Ana Belén Sanz, Alberto Ortiz
Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR)...
October 19, 2016: American Journal of Physiology. Renal Physiology
Patricio Lopez-Jaramillo
Cardiovascular diseases (CVD) are major causes of death and illness worldwide. In recent decades an increased prevalence of CVD mortality has been reported in low-medium income countries, which has been associated with changes in life styles, deficiencies in health systems and the persistence of social inequities.The metabolic syndrome comprises a cluster of cardiometabolic risk factors, with insulin resistance and increased adiposity as its central features. Identifying individuals with metabolic syndrome is important due to its association with an increased risk of coronary heart disease and type 2 diabetes mellitus (DM2)...
September 2016: Journal of Hypertension
Jiajin Yang, Heng Ge, Caroline J Poulton, Susan L Hogan, Yichun Hu, Britta E Jones, Candace D Henderson, Elizabeth A McInnis, William F Pendergraft, J Charles Jennette, Ronald J Falk, Dominic J Ciavatta
BACKGROUND: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by destructive vascular inflammation. Two prominent ANCA autoantigens are myeloperoxidase (MPO) and proteinase 3 (PR3), and transcription of MPO and PRTN3, the genes encoding the autoantigens, is associated with disease activity. We investigated whether patients with AAV have alterations in histone modifications, particularly those associated with transcriptional activation, at MPO and PRTN3...
2016: Clinical Epigenetics
Andreas Schlitzer, Joachim L Schultze
Tissue macrophages of fetal and adult origin have pivotal roles in tissue homeostasis and organ inflammation. Recently several functional and transcriptomic studies have revealed their unique module-like transcriptomic organization leading to enormous tissue-dependent functional plasticity. In this review, we discuss the development, tissue adaption and function of resident murine and human macrophages. Finally, we discuss our limited knowledge on human tissue macrophages and provide our opinion on their relevance during disease and for clinical application...
October 18, 2016: Immunology and Cell Biology
Naoshi Nishida, Masatoshi Kudo
Accumulation of genetic and epigenetic alterations is a hallmark of cancer genomes, including those in hepatocellular carcinoma (HCC). Particularly, in human HCC, epigenetic changes are more frequently observed than genetic changes in a variety of cancer-related genes, suggesting a potential role for epigenetic alterations during hepatocarcinogenesis. Several environmental factors, such as inflammation, obesity, and steatosis, are reported to affect the epigenetic status in hepatocytes, which could play a role in HCC development...
2016: Digestive Diseases
John Fenimore, Howard A Young
Interferon gamma, referred to here as IFN-γ, is a major component in immunological cell signaling and is a critical regulatory protein for overall immune system function. First discovered in 1965 (Wheelock Science 149: (3681)310-311, 1965), IFN-γ is the only Type II interferon identified. Its expression is both positively and negatively controlled by different factors. In this chapter, we will review the transcriptional and post-transcriptional control of IFN-γ expression. In the transcriptional control part, the regular activators and suppressors are summarized, we will also focus on the epigenetic control, such as chromosome access, DNA methylation, and histone acetylation...
2016: Advances in Experimental Medicine and Biology
Helena C Cesar, Luciana Pellegrini Pisani
A high-fat diet is the main environmental cue that has been studied in the hypothalamus since the discovery of its connection with hypothalamic inflammation. Current evidence shows hypothalamic inflammation as a likely mechanism for the dysregulation on the homeostatic control of energy balance, which leads to metabolic alterations and obesity. Although this mechanism seems to be reversible when set during adulthood, we argue whether dietary fatty acids, during critical periods of development, could affect hypothalamic function permanently and set an increased susceptibility to obesity...
September 13, 2016: Journal of Nutritional Biochemistry
Yu Bin Shin, Jong Hoon Park
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common inherited disorders. It is the fourth leading cause of renal replacement and renal failure worldwide. Mutations in PKD1 or PKD2 cause ADPKD. Patients with ADPKD show progressive growth of renal cysts filled with cystic fluid, leading to end-stage renal disease (ESRD) and renal failure by their sixth decade of life. Currently, there are no curative treatments for ADPKD. Therefore, patients require dialysis or kidney transplantation...
2016: Advances in Experimental Medicine and Biology
Syed O Ali, Farhaan A Khan, Miguel A Galindo-Campos, José Yélamos
Poly(ADP-ribosyl)ation (PARylation) is a widespread and highly conserved post-translational modification catalysed by a large family of enzymes called poly(ADP-ribose) polymerases (PARPs). PARylation plays an essential role in various cardinal processes of cellular physiology and recent approvals and breakthrough therapy designations for PARP inhibitors in cancer therapy have sparked great interest in pharmacological targeting of PARP proteins. Although, many PARP inhibitors have been developed, existing compounds display promiscuous inhibition across the PARP superfamily which could lead to unwanted off-target effects...
2016: American Journal of Cancer Research
Jason R Cuomo, Gyanendra K Sharma, Preston D Conger, Neal L Weintraub
Radiation-induced cardiovascular disease (RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy (RT). Cardiovascular complications include effusive or constrictive pericarditis, cardiomyopathy, valvular heart disease, and coronary/vascular disease. These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels. Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD, the increasing number of long-term cancer survivors, including those treated with older higher-dose RT regimens, will ensure a steady flow of afflicted patients for the foreseeable future...
September 26, 2016: World Journal of Cardiology
Patrícia Oliveira, Joana Carvalho, Sara Rocha, Mafalda Azevedo, Inês Reis, Vânia Camilo, Bárbara Sousa, Sofia Valente, Joana Paredes, Raquel Almeida, David Huntsman, Carla Oliveira
Dies1/VISTA induces embryonic stem-cell differentiation, via BMP-pathway, but also acts as inflammation regulator and immune-response modulator. Dies1 inhibition in a melanoma-mouse model led to increased tumour-infiltrating T-cells and decreased tumour growth, emphasizing Dies1 relevance in tumour-microenvironment. Dies1 is involved in cell de/differentiation, inflammation and cancer processes, which mimic those associated with Epithelial-to-Mesenchymal-Transition (EMT). Despite this axis linking Dies1 with EMT and cancer, its expression, modulation and relevance in these contexts is unknown...
October 10, 2016: Scientific Reports
N A Wijetunga, M Pascual, J Tozour, F Delahaye, M Alani, M Adeyeye, A W Wolkoff, A Verma, J M Greally
The predisposition of patients with Hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) involves components of viral infection, inflammation and time. The development of multifocal, genetically distinct tumours is suggestive of a field defect affecting the entire liver. The molecular susceptibility mediating such a field defect is not understood. One potential mediator of long-term cellular reprogramming is heritable (epigenetic) regulation of transcription, exemplified by DNA methylation. We studied epigenetic and transcriptional changes in HCV-infected livers in comparison with control, uninfected livers and HCC, allowing us to identify pre-neoplastic epigenetic and transcriptional events...
October 10, 2016: Oncogene
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