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Extracellular Histones

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https://www.readbyqxmd.com/read/29156107/hemodynamic-force-triggers-rapid-netosis-within-sterile-thrombotic-occlusions
#1
X Yu, J Tan, S L Diamond
BACKGROUND: Neutrophil extracellular traps (NETs) are released when neutrophils encounter infectious pathogens, especially during sepsis. Additionally, NETosis occurs during venous and arterial thrombosis, disseminated intravascular coagulation, and trauma. OBJECTIVE: We tested if hemodynamic forces trigger NETosis during sterile thrombosis. METHODS: NETs were imaged with Sytox-green during microfluidic perfusion of Factor XIIa-inhibited or thrombin-inhibited human whole blood over fibrillar collagen (± tissue factor)...
November 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29155721/visualizing-macrophage-extracellular-traps-using-confocal-microscopy
#2
Roleen Sharma, Kim M O'Sullivan, Stephen R Holdsworth, Philip G Bardin, Paul T King
A primary method used to define the presence of neutrophil extracellular traps (NETs) is confocal microscopy. We have modified established confocal microscopy methods to visualize macrophage extracellular traps (METs). These extracellular traps are defined by the presence of extracellular chromatin with co-expression of other components such as granule proteases, citrullinated histones, and peptidyl arginase deiminase (PAD). The expression of METs is generally measured after exposure to a stimulus and compared to un-stimulated samples...
October 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#3
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#4
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29137331/hdac-inhibitors-enhance-the-immunotherapy-response-of-melanoma-cells
#5
Laurence Booth, Jane L Roberts, Andrew Poklepovic, John Kirkwood, Paul Dent
We focused on the ability of the pan-histone deacetylase (HDAC) inhibitors AR42 and sodium valproate to alter the immunogenicity of melanoma cells. Treatment of melanoma cells with HDAC inhibitors rapidly reduced the expression of multiple HDAC proteins as well as the levels of PD-L1, PD-L2 and ODC, and increased expression of MHCA. In a cell-specific fashion, melanoma isolates released the immunogenic protein HMGB1 into the extracellular environment. Very similar data were obtained in ovarian and H&NSCC PDX isolates, and in established tumor cell lines from the lung and kidney...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133856/therapeutic-targeting-of-extracellular-dna-improves-the-outcome-of-intestinal-ischemic-reperfusion-injury-in-neonatal-rats
#6
Michael Boettcher, Georg Eschenburg, Stefan Mietzsch, Miguel Jiménez-Alcázar, Michaela Klinke, Deirdre Vincent, Bastian Tiemann, Robert Bergholz, Konrad Reinshagen, Tobias A Fuchs
Thrombosis and inflammation cooperate in the development of intestinal infarction. Recent studies suggest that extracellular DNA released by damaged cells or neutrophils in form of extracellular traps (NETs) contributes to organ damage in experimental models of ischemia-reperfusion injury. Here we compared the therapeutic effects of targeting fibrin or extracellular DNA in intestinal infarction after midgut volvulus in rats. Following iatrogenic midgut volvulus induction for 3 hours, we treated animals with a combination of tissue plasminogen activator (tPA) and low molecular weight heparin (LMWH) to target fibrin or with DNase1 to degrade extracellular DNA...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133350/extracellular-histones-induce-erythrocyte-fragility-and-anemia
#7
Farzaneh Kordbacheh, Connor H O'Meara, Lucy A Coupland, Patrick M Lelliott, Christopher R Parish
Extracellular histones have been shown to play an important pathogenic role in many diseases, primarily through their cytotoxicity towards nucleated cells and their ability to promote platelet activation with resultant thrombosis and thrombocytopenia. In contrast, little is known about the effect of extracellular histones on erythrocyte function. We demonstrate here that histones promote erythrocyte aggregation, sedimentation and, using a novel in vitro shear stress model, induce erythrocyte fragility and lysis in a concentration dependent manner...
November 13, 2017: Blood
https://www.readbyqxmd.com/read/29129225/lipopolysaccharide-induced-neutrophil-extracellular-trap-formation-in-canine-neutrophils-is-dependent-on-histone-h3-citrullination-by-peptidylarginine-deiminase
#8
Ronald H L Li, Geena Ng, Fern Tablin
Neutrophils release neutrophil extracellular traps (NETs), which are extracellular chromatin decorated with histones and antimicrobial proteins. Although known for antimicrobial properties, overzealous production of NETs (NETosis) may lead to cytotoxicity and multiple organ failure in sepsis. Pathogen-induced NETosis has been extensively studied in mice but its importance in dogs remains largely unknown. This study sought to characterize in vitro NETosis induced by E.coli LPS, including assessing the role of peptidylarginine deiminase (PAD) in canine NETosis...
December 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29124783/a-key-role-for-rac-and-pak-signaling-in-neutrophil-extracellular-traps-nets-formation-defines-a-new-potential-therapeutic-target
#9
M Gavillet, K Martinod, R Renella, D D Wagner, D A Williams
NET formation in mice (NETosis) is supported by reactive oxygen species (ROS) production by NADPH oxidase and histone hypercitrullination by peptidylarginine deiminase 4 (PAD4). Rac1 and Rac2, expressed in polymorphonuclear neutrophils (PMNs), regulate the cytoskeleton, cell shape, adhesion and migration and are also essential components of the NADPH oxidase complex. We aimed to explore the role of the Rac signaling pathway including the upstream guanosine exchange factor (GEF) activator, Vav, and a downstream effector, the p21-activated kinase, Pak, on NETosis in PMNs using a previously described flow-cytometry-based assay...
November 10, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29123941/bile-acids-as-global-regulators-of-hepatic-nutrient-metabolism
#10
Phillip B Hylemon, Kazuaki Takabe, Mikhail Dozmorov, Masayuki Nagahashi, Huiping Zhou
Bile acids (BA) are synthesized from cholesterol in the liver. They are essential for promotion of the absorption of lipids, cholesterol, and lipid-soluble vitamins from the intestines. BAs are hormones that regulate nutrient metabolism by activating nuclear receptors (farnesoid X receptor (FXR), pregnane X receptor, vitamin D) and G protein-coupled receptors (e.g., TGR5, sphingosine-1-phosphate receptor 2 (S1PR2)) in the liver and intestines. In the liver, S1PR2 activation by conjugated BAs activates the extracellular signal-regulated kinase 1/2 and AKT signaling pathways, and nuclear sphingosine kinase 2...
June 2017: Liver Res
https://www.readbyqxmd.com/read/29121655/experimental-blunt-chest-trauma-induced-myocardial-inflammation-and-alteration-of-gap-junction-protein-connexin-43
#11
Miriam Kalbitz, Elisa Maria Amann, Belinda Bosch, Annette Palmer, Anke Schultze, Jochen Pressmar, Birte Weber, Martin Wepler, Florian Gebhard, Hubert Schrezenmeier, Rolf Brenner, Markus Huber-Lang
OBJECTIVE: Severe blunt chest trauma in humans is associated with high mortality rates. Whereas lung tissue damage and lung inflammation after blunt chest trauma have extensively been investigated, the traumatic and posttraumatic effects on the heart remain poorly understood. Therefore, the purpose of this study was to define cardiac injury patterns in an experimental blunt chest trauma model in rats. METHODS: Experimental blunt chest trauma was induced by a blast wave in rats, with subsequent analysis of its effects on the heart...
2017: PloS One
https://www.readbyqxmd.com/read/29121457/drugs-implicated-in-systemic-autoimmunity-modulate-neutrophil-extracellular-trap-formation
#12
Jorge A Irizarry-Caro, Carmelo Carmona-Rivera, Daniella M Schwartz, Sami S Khaznadar, Mariana J Kaplan, Peter C Grayson
OBJECTIVE: Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce auto-reactivity in at-risk individuals. The study objective was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation. METHODS: Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy...
November 9, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29117594/histones-and-chymotrypsin-like-elastases-play-significant-roles-in-the-antimicrobial-activity-of-tongue-sole-neutrophil-extracellular-traps
#13
Li-Lian Wen, Ming-Li Zhao, Heng Chi, Li Sun
Neutrophil extracellular traps (NETs) are a form of extracellular antimicrobial structure of neutrophils observed in higher and lower vertebrates, the latter including the teleost fish tongue sole Cynoglossus semilaevis. However, the antimicrobial mechanism of fish NETs is unknown. In the present study, we examined the potential contribution of histones and elastases to the antibacterial effect of tongue sole NETs. For this purpose, two histones (CsH2B and CsH4) and two elastases (CsEla1 and CsEla2) of tongue sole were investigated...
November 5, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29115561/inhibition-of-histone-deacetylase-1-ameliorates-renal-tubulointerstitial-fibrosis-via-modulation-of-inflammation-and-extracellular-matrix-gene-transcription-in-mice
#14
Tùng Nguyễn-Thanh, Dal Kim, Sik Lee, Won Kim, Sung Kwang Park, Kyung Pyo Kang
Renal tubulointerstitial fibrosis is characterized by sustained inflammation and excessive extracellular matrix (ECM) accumulation, leading to chronic kidney disease. Valproic acid (VPA) has anticancer activity through regulation of cell differentiation and apoptosis via inhibition of histone deacetylase (HDAC) activity and is considered a class I HDAC inhibitor. In this study, the effect of VPA on unilateral ureteral obstruction (UUO)‑induced renal fibrosis by modulation of renal inflammation and ECM gene transcription was investigated...
October 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29107075/the-role-of-extracellular-histones-in-influenza-virus-pathogenesis
#15
Harshini K Ashar, Nathan C Mueller, Jennifer M Rudd, Timothy A Snider, Mallika Achanta, Maram Prasanthi, Sivasami Pulavendran, Paul G Thomas, Ramachandran Akhilesh, Jerry R Malayer, Jerry W Ritchey, Rachakatla Rajasekhar, Vincent Tk Chow, Charles T Esmon, Narasaraju Teluguakula
Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza...
October 26, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29102149/systemic-histone-release-disrupts-plasmalemma-and-contributes-to-necrosis-in-acute-pancreatitis
#16
Peter Szatmary, Tingting Liu, Simon T Abrams, Svetlana Voronina, Li Wen, Michael Chvanov, Wei Huang, Guozheng Wang, David N Criddle, Alexey V Tepikin, Cheng-Hock Toh, Robert Sutton
BACKGROUND: Clinical and experimental acute pancreatitis feature histone release within the pancreas from innate immune cells and acinar cell necrosis. In this study, we aimed to detail the source of circulating histones and assess their role in the pathogenesis of acute pancreatitis. METHODS: Circulating nucleosomes were measured in patient plasma, taken within 24 and 48 h of onset of acute pancreatitis and correlated with clinical outcomes. Using caerulein hyperstimulation, circulating histones were measured in portal, systemic venous and systemic arterial circulation in mice, and the effects of systemic administration of histones in this model were assessed...
October 7, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/29101790/thrombomodulin-alfa-attenuates-the-procoagulant-effect-and-cytotoxicity-of-extracellular-histones-through-the-promotion-of-protein-c-activation
#17
Keita Osada, Tatsuro Minami, Takashi Arioka, Takumi Sakai, Shunsuke Tawara, Koh Kawasaki, Jawed Fareed, Osamu Matsuzaki
INTRODUCTION: Extracellular histones are reported to increase thrombin generation in the plasma and induce endothelial cell death in vitro. These effects of histones were suggested to involve histone-induced inhibition of TM-dependent activated protein C (APC) generation. Therefore, we hypothesized that TM alfa, a recombinant human soluble TM, attenuates these effects of histones by promoting the generation of APC. In the present study, we investigated the effects of TM alfa on the histone-induced decrease in APC generation, an increase in thrombin generation, and endothelial cell death in vitro...
October 27, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29063143/the-nav1-7-blocker-protoxin-ii-reduces-burn-injury-induced-spinal-nociceptive-processing
#18
Jose Vicente Torres-Pérez, Pavel Adamek, Jiri Palecek, Marcela Vizcaychipi, Istvan Nagy, Angelika Varga
Controlling pain in burn-injured patients poses a major clinical challenge. Recent findings suggest that reducing the activity of the voltage-gated sodium channel Nav1.7 in primary sensory neurons could provide improved pain control in burn-injured patients. Here, we report that partial thickness scalding-type burn injury on the rat paw upregulates Nav1.7 expression in primary sensory neurons 3 h following injury. The injury also induces upregulation in phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), a marker for nociceptive activation in primary sensory neurons...
October 23, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29061334/neutrophil-peptidyl-arginine-deiminase-4-has-a-pivotal-role-in-ischemia-reperfusion-induced-acute%C3%A2-kidney-injury
#19
Wesley M Raup-Konsavage, Yanming Wang, Wei Wei Wang, Denis Feliers, Hong Ruan, W Brian Reeves
Ischemia/reperfusion is a common cause of acute kidney injury (AKI). However, mechanisms underlying the sudden loss in kidney function and tissue injury remain to be fully elucidated. Here, we investigated the role of peptidyl arginine deiminase-4 (PAD4), which converts arginine to citrulline and plays a role in epigenetic regulation and inflammation, in renal ischemia/reperfusion injury. PAD4 expression was highly induced in infiltrating leukocytes 24 hours following renal ischemia and reperfusion. This induction was accompanied by citrullination of histone H3 and formation of neutrophil extracellular traps in kidneys of wild-type mice...
October 20, 2017: Kidney International
https://www.readbyqxmd.com/read/29061044/ubiquitin-conjugation-probed-by-inflammation-in-myeloid-derived-suppressor-cell-extracellular-vesicles
#20
Katherine R Adams, Sitara Chauhan, Divya B Patel, Virginia K Clements, Yan Wang, Steven M Jay, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Catherine Fenselau
Ubiquitinated proteins carried by the extracellular vesicles (EV) released by myeloid-derived suppressor cells (MDSC) have been investigated using proteomic strategies to examine the effect of tumor-associated inflammation. EV were collected from MDSC directly following isolation from tumor-bearing mice with low and high inflammation. Among the 1092 proteins (high inflammation) and 925 proteins (low inflammation) identified, more than 50% were observed as ubiquitinated proteoforms. More than three ubiquitin-attachment sites were characterized per ubiquitinated protein, on average...
November 10, 2017: Journal of Proteome Research
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