Read by QxMD icon Read

Extracellular Histones

Lisa Menegazzo, Valentina Scattolini, Roberta Cappellari, Benedetta Maria Bonora, Mattia Albiero, Mario Bortolozzi, Filippo Romanato, Giulio Ceolotto, Saula Vigili de Kreutzeberg, Angelo Avogaro, Gian Paolo Fadini
AIMS: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis. METHODS: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months. To control for the effect on glucose, we also measured NET components in the plasma of patients with type 2 diabetes before and after treatment with insulin or dapagliflozin...
March 15, 2018: Acta Diabetologica
Chiaki Yoshihara-Hirata, Keisuke Yamashiro, Tadashi Yamamoto, Hiroaki Aoyagi, Hidetaka Ideguchi, Mari Kawamura, Risa Suzuki, Mitsuaki Ono, Hidenori Wake, Masahiro Nishibori, Shogo Takashiba
High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein, secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 mediates various inflammatory diseases, including periodontitis; however, the underlying mechanisms of HMGB1-induced periodontal inflammation are not completely understood. Here, we examined whether anti-HMGB1 neutralizing antibody inhibits periodontal progression and investigated the molecular pathology of HMGB1 in vitro and in vivo In vitro analysis indicated that HMGB1, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-1β (IL-1β) were secreted in response to tumor necrosis factor-α (TNF-α) stimuli in human gingival epithelial cells (HGECs) and human monocytic leukemia cells (THP-1) treated with phorbol myristate acetate...
March 12, 2018: Infection and Immunity
Silvia D Visonà, Onno J de Boer, Claire Mackaaij, Hans H de Boer, Kartika R Pertiwi, Ruben W de Winter, Antonio Osculati, Allard C van der Wal
Acute medial dissection of aorta can occur in the context of a sudden and unexpected death. For medico-legal reasons it is important to estimate as accurately the histological age of dissections. We evaluated the additional value of a systematic application of immunohistochemistry, compared with conventional histology only, in determining chronological steps of injury and repair. Thirty two paraffin embedded specimens of aortic dissection were retrospectively allocated to one of four defined stages: acute (I), subacute (II), early organizing (III) and scarring (IV) using Hematoxylin and Eosin and Elastica van Gieson stained sections...
February 10, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
K H Lee, L Cavanaugh, H Leung, F Yan, Z Ahmadi, B H Chong, F Passam
INTRODUCTION: Neutrophil extracellular traps (NETs) are networks of extracellular fibres produced from neutrophil DNA with a pathogenic role in infection, thrombosis and other conditions. Reliable assays for measuring NETs are desirable as novel treatments targeting NETs are being explored for the treatment of these conditions. We compare a whole blood flow cytometry method with serum assays to measure NETs-associated markers in patients with sepsis and thrombosis. METHODS: Patients with deep venous thrombosis (n = 25), sepsis (n = 21) and healthy controls (n = 23) were included in the study...
March 9, 2018: International Journal of Laboratory Hematology
Johannes Westman, Bhavya Chakrakodi, Johanna Snäll, Matthias Mörgelin, Martin Bruun Madsen, Ole Hyldegaard, Ariane Neumann, Inga-Maria Frick, Anna Norrby-Teglund, Lars Björck, Heiko Herwald
Innate immunity relies on an effective recognition of the pathogenic microorganism as well as on endogenous danger signals. While bacteria in concert with their secreted virulence factors can cause a number of inflammatory reactions, danger signals released at the site of infection may in addition determine the amplitude of such responses and influence the outcome of the disease. Here, we report that protein SIC, Streptococcal Inhibitor of Complement, an abundant secreted protein from Streptococcus pyogenes , binds to extracellular histones, a group of danger signals released during necrotizing tissue damage...
2018: Frontiers in Immunology
Raphaël Coscas, Sebastien Dupont, Sacha Mussot, Liliane Louedec, Harry Etienne, Marion Morvan, Gilles Chiocchia, Ziad Massy, Marie-Paule Jacob, Jean-Baptiste Michel
BACKGROUND: Recent evidence suggests that adaptive immunity develops during abdominal aortic aneurysm evolution. Uncertainties remain about the antigens implicated and their role in inducing rupture. Because antigens from the extracellular matrix (ECM) have been suspected, the aim of this experimental study was to characterize the role of adaptive immunity directed against antigens from the aortic ECM. METHODS: In a first step, an experimental model of abdominal aortic aneurysm rupture based on adaptive immunity against the ECM was developed and characterized...
March 5, 2018: Journal of Vascular Surgery
Sun-Ju Yi, Seong Yun Hwang, Myung-Ju Oh, Yang-Hoon Kim, Hojin Ryu, Sung-Keun Rhee, Byung H Jhun, Kyunghwan Kim
Signal transduction pathways regulate the gene expression by altering chromatin dynamics in response to mitogens. Ras proteins are key regulators linking extracellular stimuli to a diverse range of biological responses associated with gene regulation. In mammals, the three ras genes encode four Ras protein isoforms: H-Ras, K-Ras4A, K-Ras4B, and N-Ras. Although emerging evidence suggests that Ras isoforms differentially regulate gene expressions and are functionally nonredundant, the mechanisms underlying Ras specificity and Ras signaling effects on gene expression remain unclear...
2018: BioMed Research International
Fei Hong, Lu Wan, Jie Liu, Ke Huang, Zhenmeng Xiao, Yingjing Zhang, Chunwei Shi
Liver fibrosis is characterized by deposition of excessive extracellular matrix (ECM). The major source of ECM is activated hepatic stellate cells (HSCs). Previously, we reported that hypoxia-inducible factor-1 (Hif-1) regulates activation of HSCs through autophagy. In current work, human HSC cell line LX-2 was used as cell model. It was determined that trimethylation of H3 histone on lysine 4 (H3K4me3) occurred in the Hif-1 transcriptional complex. Inhibition of modifications of histone methylation suppressed Hif-1 nuclear transport, autophagosome formation, and activation of LX-2 cells...
March 2018: FEBS Open Bio
Yongzhi Wang, Lingtao Luo, Oscar Ö Braun, Johannes Westman, Raed Madhi, Heiko Herwald, Matthias Mörgelin, Henrik Thorlacius
Abdominal sepsis is associated with dysfunctional hemostasis. Thrombin generation (TG) is a rate-limiting step in systemic coagulation. Neutrophils can expell neutrophil extracellular traps (NETs) and/or microparticles (MPs) although their role in pathological coagulation remains elusive. Cecal ligation and puncture (CLP)-induced TG in vivo was reflected by a reduced capacity of plasma from septic animals to generate thrombin. Depletion of neutrophils increased TG in plasma from CLP mice. Sepsis was associated with increased histone 3 citrullination in neutrophils and plasma levels of cell-free DNA and DNA-histone complexes and administration of DNAse not only eliminated NET formation but also elevated TG in sepsis...
March 5, 2018: Scientific Reports
De Yang, Zhen Han, Md Masud Alam, Joost J Oppenheim
High-mobility group (HMG) nucleosome binding domain 1 (HMGN1), which previously was thought to function only as a nucleosome-binding protein that regulates chromatin structure, histone modifications, and gene expression, was recently discovered to be an alarmin that contributes extracellularly to the generation of innate and adaptive immune responses. HMGN1 promotes DC recruitment through interacting with a Gαi protein-coupled receptor (GiPCR) and activates DCs predominantly through triggering TLR4. HMGN1 preferentially promotes Th1-type immunity, which makes it relevant for the fields of vaccinology, autoimmunity, and oncoimmunology...
March 1, 2018: Seminars in Immunology
Martin Rao, Davide Valentini, Alimuddin Zumla, Markus Maeurer
BACKGROUND: New tuberculosis (TB) drug treatment regimens are urgently needed. We evaluated the potential of the histone deacetylase inhibitors (HDIs) valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) to enhance the effects of first-line TB drugs against intracellular Mycobacterium tuberculosis (M. tb). METHODS: M. tb H37Rv cultures were exposed to VPA or SAHA over six days, in the presence or absence of isoniazid (INH) and rifampicin (RIF). The efficacy of VPA and SAHA against intracellular M...
March 1, 2018: International Journal of Infectious Diseases: IJID
Fumihiko Nagano, Tomohiro Mizuno, Shuji Mizumoto, Kengo Yoshioka, Kazuo Takahashi, Naotake Tsuboi, Shoichi Maruyama, Shuhei Yamada, Tadashi Nagamatsu
Extracellular histones induce lethal thrombosis by promoting platelet aggregation, neutrophil migration, and cell injuries. Heparin, which has negative charges, can bind to extracellular histones; however, heparin strongly inhibits the activation of coagulation. Since chondroitin sulfate (CS) shows less effect on the coagulation system than heparin does, CS has the potential to become an effective drug for lethal thrombosis with high risk of bleeding. To elucidate the therapeutic mechanisms of CS in lethal thrombosis, we investigated the interaction between CS and extracellular histones...
February 28, 2018: European Journal of Pharmacology
Jan Novak, Julie Bienertová Vašků, Miroslav Souček
The human genome contains about 22 000 protein-coding genes that are transcribed to an even larger amount of messenger RNAs (mRNA). Interestingly, the results of the project ENCODE from 2012 show, that despite up to 90 % of our genome being actively transcribed, protein-coding mRNAs make up only 2-3 % of the total amount of the transcribed RNA. The rest of RNA transcripts is not translated to proteins and that is why they are referred to as "non-coding RNAs". Earlier the non-coding RNA was considered "the dark matter of genome", or "the junk", whose genes has accumulated in our DNA during the course of evolution...
2018: Vnitr̆ní Lékar̆ství
Y L Zhang, L Guan, Y M Zheng, Z M Zhao, L J Mao, S Q Li, J Y Zhao
Objective: In order to explore the role of heparan sulfate (HS) during the pathogenesis of acute respiratory distress syndrome (ARDS) , the protective effect of HS and its fragments against extracellular histones was compared. Methods: Calf thymus histones (CTH) were injected via femoral vein to induce ARDS in rats. HS, HS fragments or saline was intraperitoneally injected (10mg/kg, Q6h, 24h) to test the protective effect against CTH. The ratio of wet/dry lung weight, protein content in bronchoalveolar lavage fluid (BALF) , total leukocyte and neutrophil count in BALF were measured...
January 20, 2018: Chinese Journal of Industrial Hygiene and Occupational Diseases
Meraj A Khan, Lijy M Philip, Guillaume Cheung, Shawn Vadakepeedika, Hartmut Grasemann, Neil Sweezey, Nades Palaniyar
Neutrophils migrating from the blood (pH 7.35-7.45) into the surrounding tissues encounter changes in extracellular pH (pHe ) conditions. Upon activation of NADPH oxidase 2 (Nox), neutrophils generate large amounts of H+ ions reducing the intracellular pH (pHi ). Nevertheless, how extracellular pH regulates neutrophil extracellular trap (NET) formation (NETosis) is not clearly established. We hypothesized that increasing pH increases Nox-mediated production of reactive oxygen species (ROS) and neutrophil protease activity, stimulating NETosis...
2018: Frontiers in Medicine
Jin Zhou, Fulin Liu, Luting Yu, Dan Xu, Bin Li, Guohui Zhang, Wen Huang, Lu Li, Yuanzhen Zhang, Wei Zhang, Hui Wang
Impaired placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity which inactivates maternal glucocorticoids is associated with poor fetal growth and a higher risk of chronic diseases in adulthood. This study aimed to elucidate the epigenetically regulatory mechanism of nicotine on placental 11β-HSD2 expression. Pregnant Wistar rats were administered 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 9 to 20. The results showed that prenatal nicotine exposure increased corticosterone levels in the placenta and fetal serum, disrupted placental morphology and endocrine function, and reduced fetal bodyweight...
February 24, 2018: Toxicology and Applied Pharmacology
Barbora Konečná, Lucia Lauková, Barbora Vlková
Cell-free self-DNA or RNA may induce an immune response by activating specific sensing receptors. During pregnancy, placental nucleic acids present in the maternal circulation further activate these receptors due to the presence of unmethylated CpG islands. A higher concentration of cell-free fetal DNA is associated with pregnancy complications and a higher risk for fetal rejection. Cell-free fetal DNA originates from placental trophoblasts. It appears in different forms: free, bound to histones in nucleosomes, in neutrophil extracellular traps and in extracellular vesicles...
February 26, 2018: Scandinavian Journal of Immunology
John Eppensteiner, Robert Patrick Davis, Andrew S Barbas, Jean Kwun, Jaewoo Lee
Despite significant improvements in injury prevention and emergency response, injury-related death and morbidity continues to increase in the US and worldwide. Patients with trauma, invasive operations, anti-cancer treatment, and organ transplantation produce a host of danger signals and high levels of pro-inflammatory and pro-thrombotic mediators, such as damage-associated molecular patterns (DAMPs) and extracellular vesicles (EVs). DAMPs (e.g., nucleic acids, histone, high-mobility group box 1 protein, and S100) are molecules released from injured, stressed, or activated cells that act as endogenous ligands of innate immune receptors, whereas EVs (e...
2018: Frontiers in Immunology
Akshaya K Meher, Michael Spinosa, John P Davis, Nicolas Pope, Victor E Laubach, Gang Su, Vlad Serbulea, Norbert Leitinger, Gorav Ailawadi, Gilbert R Upchurch
OBJECTIVE: Neutrophils promote experimental abdominal aortic aneurysm (AAA) formation via a mechanism that is independent from MMPs (matrix metalloproteinases). Recently, we reported a dominant role of IL (interleukin)-1β in the formation of murine experimental AAAs. Here, the hypothesis that IL-1β-induced neutrophil extracellular trap formation (NETosis) promotes AAA was tested. APPROACH AND RESULTS: NETs were identified through colocalized staining of neutrophil, Cit-H3 (citrullinated histone H3), and DNA, using immunohistochemistry...
February 22, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Christina Lund Kidholm, Hans Christian Beck, Julie Bukh Madsen, Nikolai Bjødstrup Palstrøm, Jes Sanddal Lindholt, Lars Melholt Rasmussen
OBJECTIVE: The pathogenesis of abdominal aortic aneurysms (AAA) involves a disturbed balance of breakdown and buildup of arterial proteins. We envision that individuals with AAA carry generalized arterial protein alterations either because of effects of genetically or environmental AAA risk factors or because of compensatory changes due to signaling molecules released from the affected aneurysmal tissue. APPROACH: Protein extraction and quantitative proteome analysis by LC-MS/MS (liquid chromatography-mass spectrometry) was done on individual samples from the internal mammary artery from 11 individuals with AAA and 33 sex- and age-matched controls without AAA...
2018: PloS One
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"