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Extracellular Histones

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https://www.readbyqxmd.com/read/28222432/extracellular-hmgb1-modulates-glutamate-metabolism-associated-with-kainic-acid-induced-epilepsy-like-hyperactivity-in-primary-rat-neural-cells
#1
Yuji Kaneko, Colleen Pappas, Teresita Malapira, Fernando Ĺ Vale, Naoki Tajiri, Cesar V Borlongan
BACKGROUND/AIMS: Neuroinflammatory processes have been implicated in the pathophysiology of seizure/epilepsy. High mobility group box 1 (HMGB1), a non-histone DNA binding protein, behaves like an inflammatory cytokine in response to epileptogenic insults. Kainic acid (KA) is an excitotoxic reagent commonly used to induce epilepsy in rodents. However, the molecular mechanism by which KA-induced HMGB1 affords the initiation of epilepsy, especially the role of extracellular HMGB1 in neurotransmitter expression, remains to be elucidated...
February 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28222125/streptococcus-sanguinis-induces-neutrophil-cell-death-by-production-of-hydrogen-peroxide
#2
Ryuichi Sumioka, Masanobu Nakata, Nobuo Okahashi, Yixuan Li, Satoshi Wada, Masaya Yamaguchi, Tomoko Sumitomo, Mikako Hayashi, Shigetada Kawabata
Streptococcus is the dominant bacterial genus in the human oral cavity and a leading cause of infective endocarditis. Streptococcus sanguinis belongs to the mitis group of streptococci and produces hydrogen peroxide (H2O2) by the action of SpxB, a pyruvate oxidase. In this study, we investigated the involvement of SpxB in survival of S. sanguinis in human blood and whether bacterial H2O2 exhibits cytotoxicity against human neutrophils. Results of a bactericidal test with human whole blood revealed that the spxB mutation in S...
2017: PloS One
https://www.readbyqxmd.com/read/28220899/group-a-streptococcal-m1-protein-provides-resistance-against-the-antimicrobial-activity-of-histones
#3
Simon Döhrmann, Christopher N LaRock, Ericka L Anderson, Jason N Cole, Brinda Ryali, Chelsea Stewart, Poochit Nonejuie, Joe Pogliano, Ross Corriden, Partho Ghosh, Victor Nizet
Histones are essential elements of chromatin structure and gene regulation in eukaryotes. An unexpected attribute of these nuclear proteins is their antimicrobial activity. A framework for histone release and function in host defense in vivo was revealed with the discovery of neutrophil extracellular traps, a specialized cell death process in which DNA-based structures containing histones are extruded to ensnare and kill bacteria. Investigating the susceptibility of various Gram-positive pathogens to histones, we found high-level resistance by one leading human pathogen, group A Streptococcus (GAS)...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220120/neutrophil-extracellular-traps-and-its-implications-in-inflammation-an-overview
#4
REVIEW
Vidal Delgado-Rizo, Marco A Martínez-Guzmán, Liliana Iñiguez-Gutierrez, Alejandra García-Orozco, Anabell Alvarado-Navarro, Mary Fafutis-Morris
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209726/therapeutic-targeting-of-the-pathological-triad-of-extrasynaptic-nmda-receptor-signaling-in-neurodegenerations
#5
REVIEW
Hilmar Bading
Activation of extrasynaptic N-methyl-d-aspartate (NMDA) receptors causes neurodegeneration and cell death. The disease mechanism involves a pathological triad consisting of mitochondrial dysfunction, loss of integrity of neuronal structures and connectivity, and disruption of excitation-transcription coupling caused by CREB (cyclic adenosine monophosphate-responsive element-binding protein) shut-off and nuclear accumulation of class IIa histone deacetylases. Interdependency within the triad fuels an accelerating disease progression that culminates in failure of mitochondrial energy production and cell loss...
February 16, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28208054/high-glucose-induced-hypomethylation-promotes-binding-of-sp-1-to-myo-inositol-oxygenase-implication-in-the-pathobiology-of-diabetic-tubulopathy
#6
Isha Sharma, Rajesh K Dutta, Neel K Singh, Yashpal S Kanwar
The catabolic enzyme myo-inositol oxygenase (MIOX) is expressed in proximal tubules and up-regulated in the diabetic state. Previously, we reported its transcriptional and translation regulation by high glucose (HG), osmolytes, and fatty acids. However, its epigenetic regulation is unknown. Bisulfite sequencing revealed that both human and mouse MIOX promoters, enriched with CpG sites, are hypomethylated and unmethylated under HG ambience and hyperglycemic states associated with increased MIOX expression. Eletrophoretic mobility shift assays revealed increased binding of unmethylated oligos with nucleoproteins of cells maintained under HG...
February 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28205538/complement-component-5-promotes-lethal-thrombosis
#7
Tomohiro Mizuno, Kengo Yoshioka, Masashi Mizuno, Mie Shimizu, Fumihiko Nagano, Tomoyuki Okuda, Naotake Tsuboi, Shoichi Maruyama, Tadashi Nagamatsu, Masaki Imai
Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45-75 μg/g)...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28204821/neutrophil-extracellular-traps-induce-il-1%C3%AE-production-by-macrophages-in-combination-with-lipopolysaccharide
#8
Zhongshuang Hu, Taisuke Murakami, Hiroshi Tamura, Johannes Reich, Kyoko Kuwahara-Arai, Toshiaki Iba, Yoko Tabe, Isao Nagaoka
Upon exposure to invading microorganisms, neutrophils undergo NETosis, a recently identified type of programmed cell death, and release neutrophil extracellular traps (NETs). NETs are described as an antimicrobial mechanism, based on the fact that NETs can trap microorganisms and exhibit bactericidal activity through the action of NET‑associated components. In contrast, the components of NETs have been recognized as damage‑associated molecular pattern molecules (DAMPs), which trigger inflammatory signals to induce cell death, inflammation and organ failure...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28176948/theophylline-action-on-primary-human-bronchial-epithelial-cells-under-proinflammatory-stimuli-and-steroidal-drugs-a-therapeutic-rationale-approach
#9
Luca Gallelli, Daniela Falcone, Roberto Cannataro, Mariarita Perri, Raffaele Serra, Girolamo Pelaia, Rosario Maselli, Rocco Savino, Giuseppe Spaziano, Bruno D'Agostino
Theophylline is a natural compound present in tea. Because of its property to relax smooth muscle it is used in pharmacology for the treatment of airway diseases (ie, chronic obstructive pulmonary disease, asthma). However, this effect on smooth muscle is dose dependent and it is related to the development of side effects. Recently, an increasing body of evidence suggests that theophylline, at low concentrations, also has anti-inflammatory effects related to the activation of histone deacetylases. In this study, we evaluated the effects of theophylline alone and in combination with corticosteroids on human bronchial epithelial cells under inflammatory stimuli...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28176807/transcriptional-firing-helps-to-drive-netosis
#10
Meraj A Khan, Nades Palaniyar
Neutrophils are short-lived innate immune cells. These cells respond quickly to stimuli, and die within minutes to hours; the relevance of DNA transcription in dying neutrophils remains an enigma for several decades. Here we show that the transcriptional activity reflects the degree of DNA decondensation occurring in both NADPH oxidase 2 (Nox)-dependent and Nox-independent neutrophil extracellular trap (NET) formation or NETosis. Transcriptomics analyses show that transcription starts at multiple loci in all chromosomes earlier in the rapid Nox-independent NETosis (induced by calcium ionophore A23187) than Nox-dependent NETosis (induced by PMA)...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174211/overlapping-and-divergent-actions-of-structurally-distinct-hdac-inhibitors-in-cardiac-fibroblasts
#11
Katherine B Schuetze, Matthew S Stratton, Weston W Blakeslee, Michael F Wempe, Florence F Wagner, Edward B Holson, Yin-Ming Kuo, Andrew J Andrews, Tonya M Gilbert, Jacob M Hooker, Timothy A McKinsey
Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly impact cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiological and pathophysiological processes...
February 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28166238/integrin-dependent-cell-adhesion-to-neutrophil-extracellular-traps-through-engagement-of-fibronectin-in-neutrophil-like-cells
#12
Marcello Monti, Francesca Iommelli, Viviana De Rosa, Maria Vincenza Carriero, Roberta Miceli, Rosa Camerlingo, Giovanni Di Minno, Silvana Del Vecchio
Neutrophil extracellular traps (NETs), originally recognized as a host defense mechanism, were reported to promote thrombosis and metastatic dissemination of cancer cells. Here we tested the role of integrins α5β1 and ανβ3 in the adhesion of cancer cells to NETs. Neutrophil-like cells stimulated with calcium ionophore (A23187) were used as a stable source of cell-free NETs-enriched suspensions. Using NETs as an adhesion substrate, two human K562 cell lines, differentially expressing α5β1 and ανβ3 integrins, were subjected to adhesion assays in the presence or absence of DNAse 1, blocking antibodies against α5β1 or ανβ3, alone or in combination with DNAse 1, and Proteinase K...
2017: PloS One
https://www.readbyqxmd.com/read/28161762/validation-of-an-enzyme-linked-immunosorbent-assay-for-the-quantification-of-citrullinated-histone-h3-as-a-marker-for-neutrophil-extracellular-traps-in-human-plasma
#13
Charlotte Thålin, Maud Daleskog, Sophie Paues Göransson, Daphne Schatzberg, Julie Lasselin, Ann-Charlotte Laska, Anders Kallner, Thomas Helleday, Håkan Wallén, Mélanie Demers
There is an emerging interest in the diverse functions of neutrophil extracellular traps (NETs) in a variety of disease settings. However, data on circulating NETs rely largely upon surrogate NET markers such as cell-free DNA, nucleosomes, and NET-associated enzymes. Citrullination of histone H3 by peptidyl arginine deiminase 4 (PAD4) is central for NET formation, and citrullinated histone H3 (H3Cit) is considered a NET-specific biomarker. We therefore aimed to optimize and validate a new enzyme-linked immunosorbent assay (ELISA) to quantify the levels of H3Cit in human plasma...
February 4, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28157735/an-investigation-of-extracellular-histones-in-pig-to-baboon-organ-xenotransplantation
#14
Tao Li, Whayoung Lee, Hidetaka Hara, Cassandra Long, Mohamed Ezzelarab, David Ayares, Hai Huang, Yi Wang, David K C Cooper, Hayato Iwase
BACKGROUND: Serum (extracellular) histone levels are increased in inflammatory states and in the presence of coagulation dysfunction, eg, trauma, chemical/ischemic injury, infection. There is increasing evidence of a systemic inflammatory response associated with the presence of a pig xenograft in a nonhuman primate. We evaluated extracellular histone levels in baboons with various pig xenografts. METHODS: We measured serum histones in baboons with pig heterotopic heart (n=8), life-supporting kidney (n=5), orthotopic liver (n=4), and artery patch (n=9) grafts by ELISA...
February 3, 2017: Transplantation
https://www.readbyqxmd.com/read/28157489/cathepsin-h-mediated-degradation-of-hdac4-for-matrix-metalloproteinase-expression-in-hepatic-stellate-cells-implications-of-epigenetic-suppression-of-matrix-metalloproteinases-in-fibrosis-through-stabilization-of-class-iia-histone-deacetylases
#15
Zemin Yang, Yu Liu, Lan Qin, Pengfei Wu, Zanxian Xia, Mei Luo, Yilan Zeng, Hidekazu Tsukamoto, Zongyun Ju, Danmei Su, Han Kang, Zhixiong Xiao, Sujun Zheng, Zhongping Duan, Richard Hu, Qiang Wang, Stephen J Pandol, Yuan-Ping Han
In three-dimensional extracellular matrix, mesenchymal cells including hepatic stellate cells (HSCs) gain the ability to express matrix metalloproteinases (MMPs) on injury signals. In contrast, in myofibroblastic HSCs in fibrotic liver, many MMP genes are silenced into an epigenetically nonpermissive state. The mechanism by which the three-dimensional extracellular matrix confers the MMP genes into an epigenetically permissive state has not been well characterized. In continuation of previous work, we show here that the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts)...
February 1, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28154524/p38-sp1-sp4-hdac4-bdnf-axis-is-a-novel-molecular-pathway-of-the-neurotoxic-effect-of-the-methylmercury
#16
Natascia Guida, Giusy Laudati, Luigi Mascolo, Valeria Valsecchi, Rossana Sirabella, Carmine Selleri, Gianfranco Di Renzo, Lorella M T Canzoniero, Luigi Formisano
The molecular pathways involved in methylmercury (MeHg)-induced neurotoxicity are not fully understood. Since pan-Histone deacetylases (HDACs) inhibition has been found to revert the neurodetrimental effect of MeHg, it appeared of interest to investigate whether the pattern of HDACs isoform protein expression is modified during MeHg-induced neurotoxicity and the transcriptional/transductional mechanisms involved. SH-SY5Y neuroblastoma cells treated with MeHg 1 μM for 12 and 24 h showed a significant increase of HDAC4 protein and gene expression, whereas the HDACs isoforms 1-3, 5, and 6 were unmodified...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28143510/gastropod-derived-haemocyte-extracellular-traps-entrap-metastrongyloid-larval-stages-of-angiostrongylus-vasorum-aelurostrongylus-abstrusus-and-troglostrongylus-brevior
#17
Malin K Lange, Felipe Penagos-Tabares, Tamara Muñoz-Caro, Ulrich Gärtner, Helena Mejer, Roland Schaper, Carlos Hermosilla, Anja Taubert
BACKGROUND: Phagocyte-derived extracellular traps (ETs) were recently demonstrated mainly in vertebrate hosts as an important effector mechanism against invading parasites. In the present study we aimed to characterize gastropod-derived invertebrate extracellular phagocyte trap (InEPT) formation in response to larval stages of important canine and feline metastrongyloid lungworms. Gastropod haemocytes were isolated from the slug species Arion lusitanicus and Limax maximus, and the snail Achatina fulica, and exposed to larval stages of Angiostrongylus vasorum, Aelurostrongylus abstrusus and Troglostrongylus brevior and investigated for gastropod-derived InEPT formation...
January 31, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28137735/contact-system-activation-and-high-thrombin-generation-in-hyperthyroidism
#18
Namhee Kim, Ja-Yoon Gu, Hyun Ju Yoo, Se Eun Han, Young Il Kim, Il Seong Nam-Goong, Eun Sook Kim, Hyun Kyung Kim
Background Hyperthyroidism is associated with increased thrombotic risk. Since contact system activation through formation of neutrophil extracellular traps (NET) has emerged as an important trigger of thrombosis, we hypothesized that the contact system is activated along with active NET formation in hyperthyroidism and that their markers correlate with disease severity. Materials and Methods In 61 patients with hyperthyroidism and 40 normal controls, the levels of coagulation factors (fibrinogen, and factor VII, VIII, IX, XI, and XII), D-dimer, thrombin generation assay (TGA) markers, NET formation markers (histone-DNA complex, double-stranded DNA, neutrophil elastase), and contact system markers (activated factor XII [XIIa], high-molecular-weight kininogen [HMWK], prekallikrein, and bradykinin) were measured...
January 30, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28129888/alzheimer-s-disease-innate-immunity-gone-awry
#19
Theodore B VanItallie
Inflammation is an immune activity designed to protect the host from pathogens and noxious agents. In its low-intensity form, presence of an inflammatory process must be inferred from appropriate biomarkers. Occult neuroinflammation is not just secondary to Alzheimer's disease (AD) but may contribute to its pathogenesis and promote its progression. A leaky blood-brain barrier (BBB) has been observed in early AD and may play a role in its initiation and development. Studies of the temporal evolution of AD's biomarkers have shown that, in AD, the brain's amyloid burden correlates poorly with cognitive decline...
January 11, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28129394/characterization-of-early-phase-neutrophil-extracellular-traps-in-urinary-tract-infections
#20
Yanbao Yu, Keehwan Kwon, Tamara Tsitrin, Shiferaw Bekele, Patricia Sikorski, Karen E Nelson, Rembert Pieper
Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs...
January 2017: PLoS Pathogens
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