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Extracellular Histones

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https://www.readbyqxmd.com/read/28315487/xpln-is-modulated-by-hdac-inhibitors-and-negatively-regulates-sparc-expression-by-targeting-mtorc2-in-human-lung-fibroblasts
#1
Koichiro Kamio, Arata Azuma, Jiro Usuki, Kuniko Matsuda, Minoru Inomata, Nobuhiko Nishijima, Shioto Itakura, Hiroki Hayashi, Takeru Kashiwada, Nariaki Kokuho, Kenichiro Atsumi, Tomoyoshi Yamaguchi, Kazue Fujita, Yoshinobu Saito, Shinji Abe, Kaoru Kubota, Akihiko Gemma
Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extracellular matrix, whose expression is regulated by transforming growth factor (TGF)-β1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown...
March 14, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28303858/role-of-neutrophil-extracellular-traps-in-asthma-and-chronic-obstructive-pulmonary-disease
#2
REVIEW
Ting Liu, Fa-Ping Wang, Geng Wang, Hui Mao
OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) are representative chronic inflammatory airway diseases responsible for a considerable burden of disease. In this article, we reviewed the relationship between neutrophil extracellular traps (NETs) and chronic inflammatory airway diseases. DATA SOURCES: Articles published up to January 1, 2017, were selected from the PubMed, Ovid Medline, Embase databases, with the keywords of "asthma" or "pulmonary disease, chronic obstructive", "neutrophils" and "extracellular traps...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28272695/the-glucocorticoid-inhibits-neutrophils-formed-extracellular-traps-nets-and-suppresses-the-inflammation-caused-by-fallopian-tube-staphylococcal-infection
#3
S-X Luan, X-H Chen
OBJECTIVE: Fallopian tube can transport zygote into the uterine cavity, while inflammation may cause certain influences on the fallopian tube's function. Neutrophils formed extracellular traps (NET) can kill pathogenic microorganisms. This study intends to analyze the role of glucocorticoid in the regulation of NETs sterilization during the fallopian tube staphylococcal infection. MATERIALS AND METHODS: Rat fallopian tube staphylococcal infection model was established...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28264651/interactions-of-histatin-3-and-histatin-5-with-actin
#4
Edna Blotnick, Asaf Sol, Gilad Bachrach, Andras Muhlrad
BACKGROUND: Histatins are histidine rich polypeptides produced in the parotid and submandibular gland and secreted into the saliva. Histatin-3 and -5 are the most important polycationic histatins. They possess antimicrobial activity against fungi such as Candida albicans. Histatin-5 has a higher antifungal activity than histatin-3 while histatin-3 is mostly involved in wound healing in the oral cavity. We found that these histatins, like other polycationic peptides and proteins, such as LL-37, lysozyme and histones, interact with extracellular actin...
March 6, 2017: BMC Biochemistry
https://www.readbyqxmd.com/read/28254622/molecular-analyses-on-neospora-caninum-triggered-netosis-in-the-caprine-system
#5
R Villagra-Blanco, L M R Silva, U Gärtner, H Wagner, K Failing, A Wehrend, A Taubert, C Hermosilla
Neospora caninum is an obligate intracellular protozoan parasite causing serious reproductive disorders in large and small ruminants worldwide. Polymorphonuclear neutrophils (PMN) react against multiple invading pathogens through different mechanisms including the release of neutrophil extracellular traps (NETs). Here, in vitro interactions of caprine PMN and N. caninum tachyzoites were studied. Scanning electron microscopic- and immunofluorescence-analyses demonstrated that caprine PMN undergo NETosis upon contact with tachyzoites of N...
February 28, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28244682/extracellular-histones-disarrange-vasoactive-mediators-release-through-a-cox-nos-interaction-in-human-endothelial-cells
#6
Daniel Pérez-Cremades, Carlos Bueno-Betí, José Luis García-Giménez, José Santiago Ibañez-Cabellos, Carlos Hermenegildo, Federico V Pallardó, Susana Novella
Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone-mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose-dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml...
February 28, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28231240/galectin-3-histone-deacetylases-and-hedgehog-signaling-possible-convergent-targets-in-schistosomiasis-induced-liver-fibrosis
#7
REVIEW
Felipe Leite de Oliveira, Katia Carneiro, José Marques Brito, Mariana Cabanel, Jonathas Xavier Pereira, Ligia de Almeida Paiva, Wingkin Syn, Neil C Henderson, Marcia Cury El-Cheikh
Schistosomiasis affects approximately 240 million people in the world. Schistosoma mansoni eggs in the liver induce periportal fibrosis and hepatic failure driven by monocyte recruitment and macrophage activation, resulting in robust Th2 response. Here, we suggested a possible involvement of Galectin-3 (Gal-3), histone deacetylases (HDACs), and Hedgehog (Hh) signaling with macrophage activation during Th1/Th2 immune responses, fibrogranuloma reaction, and tissue repair during schistosomiasis. Gal-3 is highly expressed by liver macrophages (Kupffer cells) around Schistosoma eggs...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28222432/extracellular-hmgb1-modulates-glutamate-metabolism-associated-with-kainic-acid-induced-epilepsy-like-hyperactivity-in-primary-rat-neural-cells
#8
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
#9
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
#10
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
#11
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
#12
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...
March 6, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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