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https://www.readbyqxmd.com/read/29031599/interaction-of-dj-1-with-lyn-is-essential-for-ige-mediated-stimulation-of-human-mast-cells
#1
Do-Kyun Kim, Michael A Beaven, Dean D Metcalfe, Ana Olivera
BACKGROUND: DJ-1 is a redox-sensitive protein with multiple roles in cell homeostasis whose levels are altered in mast cell (MC)-related disorders. However, whether DJ-1 can regulate human MC function is unknown. OBJECTIVE: We sought to investigate the potential role of DJ-1 in the responses of human MCs to antigen stimulation. METHODS: DJ-1 was silenced in human CD34(+)-derived and LAD2 MCs using lentiviral sh-RNA constructs. Release of β-hexosaminidase, PGD2 and GM-CSF and changes in reactive oxygen species (ROS) levels were measured after FcεRI engagement...
October 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29020462/syk-inhibitor-r406-down-regulates-inflammation-in-an-in-vitro-model-of-pseudomonas-aeruginosa-infection
#2
Alaa Alhazmi, Joshua Choi, Marina Ulanova
As Pseudomonas aeruginosa infections are characterized by strong inflammation of infected tissues anti-inflammatory therapies in combination with antibiotics have been considered for the treatment of associated diseases. Syk tyrosine kinase is an important regulator of inflammatory responses, and its specific inhibition was explored as a therapeutic option in several inflammatory conditions; however, this has not been studied in bacterial infections. We used a model of in vitro infection of human monocytic cell line THP-1 and lung epithelial cell line H292 with both wild type and flagella-deficient mutant of P...
October 11, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28983472/aspartic-proteases-and-major-cell-wall-components-in-candida-albicans-trigger-the-release-of-neutrophil-extracellular-traps
#3
Marcin Zawrotniak, Oliwia Bochenska, Justyna Karkowska-Kuleta, Karolina Seweryn-Ozog, Wataru Aoki, Mitsuyoshi Ueda, Andrzej Kozik, Maria Rapala-Kozik
Neutrophils use different mechanisms to cope with pathogens that invade the host organism. The most intriguing of these responses is a release of neutrophil extracellular traps (NETs) composed of decondensed chromatin and granular proteins with antimicrobial activity. An important potential target of NETs is Candida albicans-an opportunistic fungal pathogen that employs morphological and phenotype switches and biofilm formation during contact with neutrophils, accompanied by changes in epitope exposition that mask the pathogen from host recognition...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28967793/fostamatinib-for-persistent-chronic-adult-immune-thrombocytopenia
#4
Adrian Newland, Eun-Ju Lee, Vickie McDonald, James B Bussel
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by phagocytosis and destruction of autoantibody-coated platelets via spleen tyrosine kinase (Syk)-mediated signal transduction in macrophages. Effectiveness of existing therapies varies, and even leading treatments (e.g., IVIg, splenectomy, rituximab, thrombopoietic agents) do not provide optimal management for a substantial number of patients with chronic ITP. Fostamatinib disodium is an orally-bioavailable investigational agent being developed for treatment of primary persistent/chronic adult ITP...
October 2, 2017: Immunotherapy
https://www.readbyqxmd.com/read/28966111/cationic-liposomes-suppress-intracellular-calcium-ion-concentration-increase-via-inhibition-of-pi3-kinase-pathway-in-mast-cells
#5
Yoshikazu Inoh, Aki Haneda, Satoshi Tadokoro, Satoru Yokawa, Tadahide Furuno
Cationic liposomes are commonly used as vectors to effectively introduce foreign genes (antisense DNA, plasmid DNA, siRNA, etc.) into target cells. Cationic liposomes are also known to affect cellular immunocompetences such as the mast cell function in allergic reactions. In particular, we previously showed that the cationic liposomes bound to the mast cell surface suppress the degranulation induced by cross-linking of high affinity IgE receptors in a time- and dose-dependent manner. This suppression is mediated by impairment of the sustained level of intracellular Ca(2+) concentration ([Ca(2+)]i) via inhibition of store-operated Ca(2+) entry (SOCE)...
September 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28957395/high-mrna-expression-of-splice-variant-syk-short-correlates-with-hepatic-disease-progression-in-chemonaive-lymph-node-negative-colon-cancer-patients
#6
Robert R J Coebergh van den Braak, Anieta M Sieuwerts, Raju Kandimalla, Zarina S Lalmahomed, Sandra I Bril, Anne van Galen, Marcel Smid, Katharina Biermann, J Han J M van Krieken, Wigard P Kloosterman, John A Foekens, Ajay Goel, John W M Martens, Jan N M IJzermans
OBJECTIVE: Overall and splice specific expression of Spleen Tyrosine Kinase (SYK) has been posed as a marker predicting both poor and favorable outcome in various epithelial malignancies. However, its role in colorectal cancer is largely unknown. The aim of this study was to explore the prognostic role of SYK in three cohorts of colon cancer patients. METHODS: Total messenger RNA (mRNA) expression of SYK, SYK(T), and mRNA expression of its two splice variants SYK short (S) and SYK long (L) were measured using quantitative reverse transcriptase (RT-qPCR) in 240 primary colon cancer patients (n = 160 patients with chemonaive lymph node negative [LNN] and n = 80 patients with adjuvant treated lymph node positive [LNP] colon cancer) and related to microsatellite instability (MSI), known colorectal cancer mutations, and disease-free (DFS), hepatic metastasis-free (HFS) and overall survival (OS)...
2017: PloS One
https://www.readbyqxmd.com/read/28949404/the-role-of-syk-i%C3%A4-b-%C3%AE-nf-%C3%A4-b-pathway-activation-in-the-reversal-effect-of-bay-61-3606-a-selective-syk-inhibitor-on-hypotension-and-inflammation-in-a-rat-model-of-zymosan-induced-non-septic-shock
#7
Demet Unsal, Meltem Kacan, Meryem Temiz-Resitoglu, Demet Sinem Guden, Belma Korkmaz, A Nihal Sari, C Kemal Buharalioglu, Hatice Yildirim-Yaroglu, Lulufer Tamer-Gumus, Bahar Tunctan, Kafait U Malik, Seyhan Sahan-Firat
Spleen tyrosine kinase (Syk), a non-receptor tyrosine kinase, plays an important role in allergic diseases and inflammation. Syk triggers several intracellular signalling cascades including Toll-like receptor signalling to activate inflammatory responses following fungal infection but the role of this enzyme in zymosan (ZYM)-induced non-septic shock and its impacts on hypotension and inflammation in rats is not well understood. This study was conducted to determine the effects of Syk inhibition on ZYM-induced alterations in the expression and/or activities of Syk, inhibitor ĸB (IĸB)-α, and nuclear factor-ĸB (NF-ĸB) p65...
September 26, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28948613/protein-tyrosine-phosphatase-ptpn22-regulates-il-1%C3%AE-dependent-th17-responses-by-modulating-dectin-1-signaling-in-mice
#8
Harriet A Purvis, Fiona Clarke, Christine K Jordan, Cristina Sanchez Blanco, Georgina H Cornish, Xuezhi Dai, David J Rawlings, Rose Zamoyska, Andrew P Cope
A single nucleotide polymorphism within the PTPN22 gene is a strong genetic risk factor predisposing to the development of multiple autoimmune diseases. PTPN22 regulates Syk and Src family kinases downstream of immuno-receptors. Fungal β-glucan receptor dectin-1 signals via Syk, and dectin-1 stimulation induces arthritis in mouse models. We investigated whether PTPN22 regulates dectin-1 dependent immune responses. Bone marrow derived dendritic cells (BMDCs) generated from C57BL/6 wild type (WT) and Ptpn22(-/-) mutant mice, were pulsed with OVA323-339 and the dectin-1 agonist curdlan and co-cultured in vitro with OT-II T-cells or adoptively transferred into OT-II mice, and T-cell responses were determined by immunoassay...
September 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28943470/eosinophils-release-extracellular-dna-traps-in-response-to-aspergillus-fumigatus
#9
Valdirene S Muniz, Juliana C Silva, Yasmim A V Braga, Rossana C N Melo, Shigeharu Ueki, Masahide Takeda, Akira Hebisawa, Koichiro Asano, Rodrigo T Figueiredo, Josiane S Neves
BACKGROUND: Eosinophils mediate the immune response in different infection conditions. The release of extracellular DNA traps (ETs) by leukocytes has been described as an innate immune response mechanism that is relevant in many disorders including fungal diseases. Different stimuli induce human eosinophil ETs (EETs) release. Aspergillus fumigatus (A. fumigatus) is an opportunistic fungus that may cause eosinophilic allergic bronchopulmonary aspergillosis (ABPA). It has been reported that eosinophils are important to the clearance of A...
September 21, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28943410/loss-of-reelin-protects-mice-against-arterial-thrombosis-by-impairing-integrin-activation-and-thrombus-formation-under-high-shear-conditions
#10
Nina Sarah Gowert, Irena Krüger, Meike Klier, Lili Donner, Friederike Kipkeew, Michael Gliem, Nicholas J Bradshaw, David Lutz, Sabrina Köber, Harald Langer, Sebastian Jander, Kerstin Jurk, Michael Frotscher, Carsten Korth, Hans H Bock, Margitta Elvers
Reelin is a secreted glycoprotein and essential for brain development and plasticity. Recent studies provide evidence that Reelin modifies platelet actin cytoskeletal dynamics. In this study we sought to dissect the contribution of Reelin in arterial thrombus formation. Here we analyzed the impact of Reelin in arterial thrombosis ex vivo and in vivo using Reelin deficient (reeler) and wildtype mice. We found that Reelin is secreted upon platelet activation and mediates signaling via glycoprotein (GP)Ib, the amyloid precursor protein (APP) and apolipoprotein E receptor 2 (ApoER2) to induce activation of Akt, extracellular signal-regulated kinase (Erk), SYK and Phospholipase Cγ2...
September 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28938395/aldose-reductase-mediates-nlrp3-inflammasome-initiated-innate-immune-response-in-hyperglycemia-induced-thp1-monocytes-and-male-mice
#11
Pabitra B Pal, Himangshu Sonowal, Kirtikar Shukla, Satish K Srivastava, Kota V Ramana
Despite recent studies that show oxidative stress-generated reactive oxygen species (ROS) regulate NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated innate immune response in various diabetic complications, the mechanism by which ROS activate innate immune response is not well understood. We have shown previously that aldose reductase (AR), besides reducing glucose, reduces lipid aldehydes and their glutathione conjugates and participates in various oxidative stress-induced inflammatory pathways...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28935670/the-bacterial-meta-cleavage-hydrolase-ligy-belongs-to-the-amidohydrolase-superfamily-not-to-the-%C3%AE-%C3%AE-hydrolase-superfamily
#12
Eugene Kuatsjah, Anson C K Chan, Marek J Kobylarz, Michael E P Murphy, Lindsay D Eltis
Strain SYK-6 of the bacterium Sphingobium sp. catabolizes lignin-derived biphenyl via a meta-cleavage pathway. In this pathway, LigY is proposed to catalyze the hydrolysis of the meta-cleavage product (MCP) 4,11-dicarboxy-8-hydroxy-9-methoxy-2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate. Here, we validated this reaction by identifying 5-carboxyvanillate and 4-carboxy-2-hydroxypenta-2,4-dienoate as the products, and determined the kcat and kcat/K m values of 9.3 ± 0.6 s(-1) and 2.5 ± 0.2 × 10(7) M(-1)s(-1), respectively...
September 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28933554/rational-targeting-of-cellular-cholesterol-in-diffuse-large-b-cell-lymphoma-dlbcl-enabled-by-functional-lipoprotein-nanoparticles-a-therapeutic-strategy-dependent-on-cell-of-origin
#13
Jonathan S Rink, Shuo Yang, Osman Cen, Tim Taxter, Kaylin M McMahon, Sol Misener, Amir Behdad, Richard Longnecker, Leo I Gordon, C Shad Thaxton
Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1)...
October 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28928455/polydatin-inhibits-mast-cell-mediated-allergic-inflammation-by-targeting-pi3k-akt-mapk-nf-%C3%AE%C2%BAb-and-nrf2-ho-1-pathways
#14
Jing Ye, Hongmei Piao, Jingzhi Jiang, Guangyu Jin, Mingyu Zheng, Jinshi Yang, Xiang Jin, Tianyi Sun, Yun Ho Choi, Liangchang Li, Guanghai Yan
Polydatin(PD) shows anti-allergic inflammatory effect, and this study investigated its underlying mechanisms in in vitro and in vivo models. IgE-mediated passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA) models were used to confirm PD effect in vivo. Various signaling pathway proteins in mast cell were examined. RT-PCR, ELISA and western blotting were applied when appropriate. Activity of Lyn and Fyn kinases in vitro was measured using the Kinase Enzyme System. PD dose-dependently reduced the pigmentation of Evans blue in the PCA model and decreased the concentration of serum histamine in PSA model, and attenuated the degranulation of mast cells without generating cytotoxicity...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919467/distribution-of-spleen-tyrosine-kinase-and-tau-phosphorylated-at-tyrosine-18-in-a-mouse-model-of-tauopathy-and-in-the-human-hippocampus
#15
Christoph Köhler, Vivien Timpa, Maja Dinekov
PURPOSE: Spleen tyrosine kinase (Syk) has been shown to phosphorylate tyrosine 18 of tau in vitro. It has been proposed that increased immunoreactivity for double-phosphorylated Syk in hippocampal neurons of Alzheimer's disease cases indicates a not yet defined neurodegenerative process. To investigate this possibility we have studied Syk and tau phosphorylated at tyrosine 18 (pTyr18) in transgenic mice and human hippocampi. METHODS: We performed immunohistochemistry, immunofluorescence labeling and Western blotting and compared the distribution of Syk double-phosphorylated at tyrosines 525 and 526 and pTyr18 in human tau transgenic pR5 mice and human hippocampi with low and high Braak stages for neurofibrillary tangle pathology...
September 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28915273/longitudinal-co-variations-between-inflammatory-cytokines-lung-function-and-patient-reported-outcomes-in-patients-with-asthma
#16
Karin Lodin, Mats Lekander, Jörgen Syk, Kjell Alving, Predrag Petrovic, Anna Andreasson
BACKGROUND: Asthma is a chronic inflammatory respiratory disorder associated with reduced lung function and poor quality of life. The condition is also associated with poor self-rated health, a major predictor of objective health trajectories. Of biological correlates to self-rated health, evidence suggests a role for inflammatory cytokines and related sickness behaviours. However, this is mainly based on cross-sectional data, and the relation has not been investigated in patients with chronic inflammatory conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28913864/strand-displacement-in-coiled-coil-structures-controlled-induction-and-reversal-of-proximity
#17
Katharina Gröger, Georgina Gavins, Oliver Seitz
Coiled-coil peptides are frequently used to create new function upon self-assembly of supramolecular complexes. A multitude of coil peptide sequences provides control over specificity and stability of coiled-coil complexes. However, comparably little attention has been paid to the development of methods that allow for the reversal of complex formation under non-denaturing conditions. Herein, we present a reversible 2-state switching system. The process involves two peptide molecules for formation of a size-mismatched coiled-coil duplex and a third, disruptor peptide which targets an overhanging end...
September 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28904407/syk-dependent-tyrosine-phosphorylation-of-3bp2-is-required-for-optimal-fcr%C3%AE-mediated-phagocytosis-and-chemokine-expression-in-u937-cells
#18
Kazuyasu Chihara, Yuji Kato, Hatsumi Yoshiki, Kenji Takeuchi, Shigeharu Fujieda, Kiyonao Sada
The adaptor protein c-Abl SH3 domain binding protein-2 (3BP2) is tyrosine phosphorylated by Syk in response to cross-linking of antigen receptors, which in turn activates various immune responses. Recently, a study using the mouse model of cherubism, a dominant inherited disorder caused by mutations in the gene encoding 3BP2, showed that 3BP2 is involved in the regulation of phagocytosis mediated by Fc receptor for IgG (FcγR) in macrophages. However, the molecular mechanisms underlying 3BP2-mediated regulation of phagocytosis and the physiological relevance of 3BP2 tyrosine phosphorylation remains elusive...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28891650/asiaticoside-mitigates-the-allergic-inflammation-by-abrogating-the-degranulation-of-mast-cells
#19
Jing Zhi Jiang, Jing Ye, Guang Yu Jin, Hong Mei Piao, Hong Cui, Ming Yu Zheng, Jin Shi Yang, Nan Che, Yun Ho Choi, Liang Chang Li, Guang Hai Yan
The effects of asiaticoside (AS) on allergic responses mediated by mast cells were investigated. AS showed no obvious cytotoxicity on RPMCs (rat peritoneal mast cells). AS reduced the intracellular calcium in RPMCs and deprived the histamine release and degranulation. AS also decreased the generation of antigen-induced tumor necrosis factor α, interleukin (IL)-4, IL-8, and IL-1β in RBL-2H3 cells sensitized by IgE. The suppression of AS on pro-inflammatory cytokines was related with the activation of the intracellular FcεRI and the inhibition of the nuclear factor-κB signaling pathway...
September 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28888895/regulation-of-platelet-activation-and-thrombus-formation-by-reactive-oxygen-species
#20
Jianlin Qiao, Jane F Arthur, Elizabeth E Gardiner, Robert K Andrews, Lingyu Zeng, Kailin Xu
Reactive oxygen species (ROS) are generated within activated platelets and play an important role in regulating platelet responses to collagen and collagen-mediated thrombus formation. As a major collagen receptor, platelet-specific glycoprotein (GP)VI is a member of the immunoglobulin (Ig) superfamily, with two extracellular Ig domains, a mucin domain, a transmembrane domain and a cytoplasmic tail. GPVI forms a functional complex with the Fc receptor γ-chain (FcRγ) that, following receptor dimerization, signals via an intracellular immunoreceptor tyrosine-based activation motif (ITAM), leading to rapid activation of Src family kinase signaling pathways...
September 7, 2017: Redox Biology
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