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https://www.readbyqxmd.com/read/27835611/effect-of-cobalt-mediated-toll-like-receptor-4-activation-on-inflammatory-responses-in-endothelial-cells
#1
Sami A Anjum, Helen Lawrence, James P Holland, John A Kirby, David J Deehan, Alison J Tyson-Capper
Cobalt-containing metal-on-metal hip replacements are associated with adverse reactions to metal debris (ARMD), including inflammatory pseudotumours, osteolysis, and aseptic implant loosening. The exact cellular and molecular mechanisms leading to these responses are unknown. Cobaltions (Co2+) activate human Toll-like receptor 4 (TLR4), an innate immune receptor responsible for inflammatory responses to Gram negative bacterial lipopolysaccharide (LPS).We investigated the effect of Co2+-mediated TLR4 activation on human microvascular endothelial cells (HMEC-1), focusing on the secretion of key inflammatory cytokines and expression of adhesion molecules...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27680514/mutational-profiling-of-a-monomac-syndrome-family-with-gata2-deficiency
#2
L-W Ding, T Ikezoe, K-T Tan, M Mori, A Mayakonda, W Chien, D-C Lin, Y-Y Jiang, M Lill, H Yang, Q-Y Sun, H P Koeffler
No abstract text is available yet for this article.
October 21, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27548265/vaccine-mediated-activation-of-human-tlr4-is-affected-by-modulation-of-culture-conditions-during-whole-cell-pertussis-vaccine-preparation
#3
Marieke E Hoonakker, Lisa M Verhagen, Elder Pupo, Alex de Haan, Bernard Metz, Coenraad F M Hendriksen, Wanda G H Han, Arjen Sloots
The potency of whole-cell pertussis (wP) vaccines is still determined by an intracerebral mouse protection test. To allow development of suitable in vitro alternatives to this test, insight into relevant parameters to monitor the consistency of vaccine quality is essential. To this end, a panel of experimental wP vaccines of varying quality was prepared by sulfate-mediated suppression of the BvgASR master virulence regulatory system of Bordetella pertussis during cultivation. This system regulates the transcription of a range of virulence proteins, many of which are considered important for the induction of effective host immunity...
2016: PloS One
https://www.readbyqxmd.com/read/27436590/pulmonary-epithelial-cancer-cells-and-their-exosomes-metabolize-myeloid-cell-derived-leukotriene-c4-to-leukotriene-d4
#4
Ana Lukic, Jie Ji, Helena Idborg, Bengt Samuelsson, Lena Palmberg, Susanne Gabrielsson, Olof Rådmark
Leukotrienes (LTs) play major roles in lung immune responses, and LTD4 is the most potent agonist for cysteinyl LT1, leading to bronchoconstriction and tissue remodeling. Here, we studied LT crosstalk between myeloid cells and pulmonary epithelial cells. Monocytic cells (Mono Mac 6 cell line, primary dendritic cells) and eosinophils produced primarily LTC4 In coincubations of these myeloid cells and epithelial cells, LTD4 became a prominent product. LTC4 released from the myeloid cells was further transformed by the epithelial cells in a transcellular manner...
September 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27235343/tlr4-induces-ccr7-dependent-monocytes-transmigration-through-the-blood-brain-barrier
#5
Alexandre Paradis, Stéphane Bernier, Nancy Dumais
In this study, we examined whether bacterial pathogen-associated molecular patterns recognized by toll-like receptors (TLRs) can modify the CCR7-dependent migration of human monocytes. MonoMac-1 (MM-1) cells and freshly isolated human monocytes were cultivated in the presence of agonists for TLR4 (which senses lipopolysaccharides from gram-negative bacteria), TLR1/2 (which senses peptidoglycan from gram-positive bacteria), and TLR9 (which recognizes bacterial DNA rich in unmethylated CpG DNA). CCR7 mRNA transcription was measured using quantitative reverse transcription polymerase chain reaction and protein expression was examined using flow cytometry...
June 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27232273/acute-lymphoblastic-leukemia-in-a-patient-with-monomac-syndrome-gata2-haploinsufficiency
#6
Ashley K Koegel, Inga Hofmann, Kristin Moffitt, Barbara Degar, Christine Duncan, Venée N Tubman
Patients with GATA2 haploinsufficiency have a significant predisposition to developing cytopenias, unique infectious manifestations, and myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). We report a unique case of a patient who presented with B-cell acute lymphoblastic leukemia (B-ALL) and was subsequently diagnosed with monocytopenia and mycobacterium avium complex (MonoMAC) syndrome/GATA2 haploinsufficiency. The development of MDS/AML in patients with GATA2 haploinsufficiency is well described, however, the development of ALL has not been reported in the literature...
October 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27001537/excreted-cytoplasmic-proteins-contribute-to-pathogenicity-in-staphylococcus-aureus
#7
Patrick Ebner, Janina Rinker, Minh Thu Nguyen, Peter Popella, Mulugeta Nega, Arif Luqman, Birgit Schittek, Moreno Di Marco, Stefan Stevanovic, Friedrich Götz
Excretion of cytoplasmic proteins in pro- and eukaryotes, also referred to as "nonclassical protein export," is a well-known phenomenon. However, comparatively little is known about the role of the excreted proteins in relation to pathogenicity. Here, the impact of two excreted glycolytic enzymes, aldolase (FbaA) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), on pathogenicity was investigated in Staphylococcus aureus Both enzymes bound to certain host matrix proteins and enhanced adherence of the bacterial cells to host cells but caused a decrease in host cell invasion...
June 2016: Infection and Immunity
https://www.readbyqxmd.com/read/26834239/functional-and-molecular-characterization-of-mouse-gata2-independent-hematopoietic-progenitors
#8
Polynikis Kaimakis, Emma de Pater, Christina Eich, Parham Solaimani Kartalaei, Mari-Liis Kauts, Chris S Vink, Reinier van der Linden, Martine Jaegle, Tomomasa Yokomizo, Dies Meijer, Elaine Dzierzak
The Gata2 transcription factor is a pivotal regulator of hematopoietic cell development and maintenance, highlighted by the fact that Gata2 haploinsufficiency has been identified as the cause of some familial cases of acute myelogenous leukemia/myelodysplastic syndrome and in MonoMac syndrome. Genetic deletion in mice has shown that Gata2 is pivotal to the embryonic generation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). It functions in the embryo during endothelial cell to hematopoietic cell transition to affect hematopoietic cluster, HPC, and HSC formation...
March 17, 2016: Blood
https://www.readbyqxmd.com/read/26716079/young-woman-with-mild-bone-marrow-dysplasia-gata2-and-asxl1-mutation-treated-with-allogeneic-hematopoietic-stem-cell-transplantation
#9
Anna Lübking, Sebastian Vosberg, Nikola P Konstandin, Annika Dufour, Alexander Graf, Stefan Krebs, Helmut Blum, Axel Weber, Stig Lenhoff, Mats Ehinger, Karsten Spiekermann, Philipp A Greif, Jörg Cammenga
Heterozygous mutations in GATA2 underlie different syndromes, previously described as monocytopenia and mycobacterial avium complex infection (MonoMAC); dendritic cell, monocytes, B- and NK lymphocytes deficiency (DCML); lymphedema, deafness and myelodysplasia (Emberger syndrome) and familiar myelodysplastic syndrome/acute myeloid leukemia (MDS / AML). Onset and severity of clinical symptoms vary and preceding cytopenias are not always present. We describe a case of symptomatic DCML deficiency and rather discrete bone marrow findings due to GATA2 mutation...
2015: Leukemia Research Reports
https://www.readbyqxmd.com/read/26710799/altered-chemotactic-response-to-cxcl12-in-patients-carrying-gata2-mutations
#10
Anna Maciejewski-Duval, Floriane Meuris, Alexandre Bignon, Marie-Laure Aknin, Karl Balabanian, Laurence Faivre, Marlène Pasquet, Vincent Barlogis, Claire Fieschi, Christine Bellanné-Chantelot, Jean Donadieu, Géraldine Schlecht-Louf, Viviana Marin-Esteban, Françoise Bachelerie
GATA2 deficiency-formerly described as MonoMAC syndrome; dendritic cells, monocytes, B cells, and natural killer cell deficiency; familial myelodysplastic syndrome/acute myeloid leukemia; or Emberger syndrome-encompasses a range of hematologic and nonhematologic anomalies, mainly characterized by monocytopenia, B lymphopenia, natural killer cell cytopenia, neutropenia, immunodeficiency, and a high risk of developing acute myeloid leukemia. Herein, we present 7 patients with GATA2 deficiency recruited into the French Severe Chronic Neutropenia Registry, which enrolls patients with all kinds of congenital neutropenia...
June 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/26460250/characterization-of-hematopoietic-gata-transcription-factor-expression-in-mouse-and-human-dendritic-cells
#11
Maaike R Scheenstra, Vishal Salunkhe, Iris M De Cuyper, Mark Hoogenboezem, Eveline Li, Taco W Kuijpers, Timo K van den Berg, Laura Gutiérrez
Dendritic cells (DCs) are key initiators and regulators of the immune response. The development of the DC lineage and their subsets requires an orchestrated regulation of their transcriptional program. Gata1, a transcription factor expressed in several hematopoietic cell lineages, has been recently reported to be required for mouse DC development and function. In humans, GATA1 is involved in the lineage separation between monocyte-derived DCs and Langerhans cells (LC) and loss of GATA1 results in differentiation arrest at the monocyte stage...
December 2015: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/26457672/endotoxin-tolerance-inhibits-lyn-and-c-src-phosphorylation-and-association-with-toll-like-receptor-4-but-increases-expression-and-activity-of-protein-phosphatases
#12
Yanbao Xiong, Michael Murphy, Tissa T Manavalan, Goutham Pattabiraman, Fu Qiu, Hui-Hsin Chang, I-Cheng Ho, Andrei E Medvedev
Endotoxin tolerance protects the host by limiting excessive 'cytokine storm' during sepsis, but compromises the ability to counteract infections in septic shock survivors. It reprograms Toll-like receptor (TLR) 4 responses by attenuating the expression of proinflammatory cytokines without suppressing anti-inflammatory and antimicrobial mediators, but the mechanisms of reprogramming remain unclear. In this study, we demonstrate that the induction of endotoxin tolerance in human monocytes, THP-1 and MonoMac-6 cells inhibited lipopolysaccharide (LPS)-mediated phosphorylation of Lyn, c-Src and their recruitment to TLR4, but increased total protein phosphatase (PP) activity and the expression of protein tyrosine phosphatase (PTP) 1B, PP2A, PTP nonreceptor type (PTPN) 22 and mitogen-activated protein kinase phosphatase (MKP)-1...
2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/26325290/high-throughput-sirna-screening-to-reveal-gata-2-upstream-transcriptional-mechanisms-in-hematopoietic-cells
#13
Yo Saito, Tohru Fujiwara, Keiichi Ohashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Kenichi Ishizawa, Hideo Harigae
Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in both hematopoietic stem and progenitor cells and is essential for cell proliferation, survival, and differentiation. Recently, evidence from studies of aplastic anemia, MonoMAC syndrome, and lung cancer has demonstrated a mechanistic link between GATA-2 and human pathophysiology. GATA-2-dependent disease processes have been extensively analyzed; however, the transcriptional mechanisms upstream of GATA-2 remain less understood...
2015: PloS One
https://www.readbyqxmd.com/read/26310831/pellino-3-promotes-endotoxin-tolerance-and-acts-as-a-negative-regulator-of-tlr2-and-tlr4-signaling
#14
Michael B Murphy, Yanbao Xiong, Goutham Pattabiraman, Tissa T Manavalan, Fu Qiu, Andrei E Medvedev
Development of endotoxin tolerance in macrophages during sepsis reprograms Toll-like receptor 4 signaling to inhibit proinflammatory cytokines without suppressing anti-inflammatory and antimicrobial mediators and protects the host from excessive inflammation and tissue damage. However, endotoxin tolerance renders septic patients immunocompromised and unable to control secondary infections. Although previous studies have revealed the importance of several negative regulators of Toll-like receptor signaling in endotoxin tolerance, the role of Pellino proteins has not been addressed...
December 2015: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/26283693/tandem-benzophenone-amino-pyridines-potent-and-selective-inhibitors-of-human-leukotriene-c4-synthase
#15
Thea K Kleinschmidt, Martin Haraldsson, Devaraj Basavarajappa, Erik Lundeberg, Madhuranayaki Thulasingam, Maria Ekoff, Alexander Fauland, Christoph Lehmann, Astrid S Kahnt, Lennart Lindbom, Jesper Z Haeggström
Cysteinyl leukotrienes (cys-LTs) are lipid mediators of inflammation. The enzyme catalyzing synthesis of cys-LTs, leukotriene C4 synthase (LTC4S), is considered an important drug target. Here we report the synthesis and characterization of three tandem benzophenone amino pyridines as inhibitors of LTC4S in vitro and in vivo. The inhibitors were characterized in vitro using recombinant human LTC4S, MonoMac 6 cells, and a panel of peripheral human immune cells. In vivo, the compounds were tested in the Zymosan A-induced peritonitis mouse model...
October 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/26210507/combating-highly-resistant-emerging-pathogen-mycobacterium-abscessus-and-mycobacterium-tuberculosis-with-novel-salicylanilide-esters-and-carbamates
#16
Zsuzsa Baranyai, Martin Krátký, Jarmila Vinšová, Nóra Szabó, Zsuzsanna Senoner, Kata Horváti, Jiřina Stolaříková, Sándor Dávid, Szilvia Bősze
In the Mycobacterium genus over one hundred species are already described and new ones are periodically reported. Species that form colonies in a week are classified as rapid growers, those requiring longer periods (up to three months) are the mostly pathogenic slow growers. More recently, new emerging species have been identified to lengthen the list, all rapid growers. Of these, Mycobacterium abscessus is also an intracellular pathogen and it is the most chemotherapy-resistant rapid-growing mycobacterium...
August 28, 2015: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/26082489/pellino-1-positively-regulates-toll-like-receptor-tlr-2-and-tlr4-signaling-and-is-suppressed-upon-induction-of-endotoxin-tolerance
#17
Michael Murphy, Yanbao Xiong, Goutham Pattabiraman, Fu Qiu, Andrei E Medvedev
Endotoxin tolerance reprograms Toll-like receptor (TLR) 4-mediated macrophage responses by attenuating induction of proinflammatory cytokines while retaining expression of anti-inflammatory and antimicrobial mediators. We previously demonstrated deficient TLR4-induced activation of IL-1 receptor-associated kinase (IRAK) 4, IRAK1, and TANK-binding kinase (TBK) 1 as critical hallmarks of endotoxin tolerance, but mechanisms remain unclear. In this study, we examined the role of the E3 ubiquitin ligase Pellino-1 in endotoxin tolerance and TLR signaling...
July 31, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25739845/rheumatologic-manifestations-of-the-monomac-syndrome-a-systematic-review
#18
REVIEW
Jennifer A Johnson, Steven S Yu, Michael Elist, Daniel Arkfeld, Richard S Panush
MonoMAC syndrome is characterized by monocytopenia with susceptibility to nontuberculous mycobacterial infections. First recognized in 2011, it is caused by GATA2 mutations and can manifest as disseminated mycobacterial, fungal, and viral infections. While mortality rates for this disorder have been high, it has recently been successfully treated with haploidentical allogeneic stem cell transplant. Since approximately one third of patients may have rheumatologic symptoms, such as erythema nodosum, panniculitis, or arthralgias, rheumatologists may expect to encounter this newly described entity with increasing frequency...
September 2015: Clinical Rheumatology
https://www.readbyqxmd.com/read/25619630/spectrum-of-myeloid-neoplasms-and-immune-deficiency-associated-with-germline-gata2-mutations
#19
REVIEW
Muhammad A Mir, Samith T Kochuparambil, Roshini S Abraham, Vilmarie Rodriguez, Matthew Howard, Amy P Hsu, Amie E Jackson, Steven M Holland, Mrinal M Patnaik
Guanine-adenine-thymine-adenine 2 (GATA2) mutated disorders include the recently described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms), congenital neutropenia, congenital lymphedema (Emberger's syndrome), sensorineural deafness, viral warts, and a spectrum of aggressive infections seen across all age groups. While considerable efforts have been made to identify the mutations that characterize this disorder, pathogenesis remains a work in progress with less than 100 patients described in current literature...
April 2015: Cancer Medicine
https://www.readbyqxmd.com/read/25591147/granulomatous-lung-disease-in-a-patient-with-a-family-history-of-hematological-disorders
#20
M J Overbeek, A A van de Loosdrecht, A Vonk-Noordegraaf
A 29-year old patient presented with granulomatous lung disease and a family history of myelodysplastic syndrome/acute myeloid leukemia. She appeared to be a carrier of a mutation in the transcription factor GATA2. The case adds to the recent described heterogeneous clinical manifestations and syndromes in which, against a background of hematologic disorders, GATA2 mutations have been demonstrated, such as the Monomac and Emberger syndromes. In patients with a granulomatous disease and a history of (familial) hematologic disorders, the occurence of GATA2 mutations should be considered, as to gain further insight in the occurrence of granulomatous disease in a possible distinct phenotype among GATA2 mutation carriers...
2014: Sarcoidosis, Vasculitis, and Diffuse Lung Diseases: Official Journal of WASOG
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