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Spleen tyrosine kinase

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https://www.readbyqxmd.com/read/29137391/activated-spleen-tyrosine-kinase-promotes-malignant-progression-of-oral-squamous-cell-carcinoma-via-mtor-s6-signaling-pathway-in-an-erk1-2-independent-manner
#1
Pan Gao, Xianghe Qiao, Haibin Sun, Yi Huang, Jie Lin, Longjiang Li, Xiaoyi Wang, Chunjie Li
Spleen tyrosine kinase (SYK), a non-receptor cytoplasmic tyrosine enzyme, is well known for its ability in certain pathways through immune receptors. Recently, SYK role in cancer has been widely studied. SYK plays a dual role as a tumor suppressor and tumor promoter. Nevertheless, its role in oral squamous cell carcinoma (OSCC) has not been fully investigated. In the current study, samples from OSCC tumors and adjacent normal counterparts were collected and SYK expression was evaluated by real-time qPCR. SYK mRNA expression in tumors was higher than the normal tissues...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29125705/m-tuberculosis-mce3c-promotes-mycobacteria-entry-into-macrophages-through-activation-of-%C3%AE-2-integrin-mediated-signaling-pathway
#2
Yong Zhang, Jie Li, Bingxi Li, Jing Wang, Cui Hua Liu
Establishment of infection by facultative intracellular pathogen Mycobacterium tuberculosis (Mtb) requires adherence to and internalization by macrophages. However, the effector molecules exploited by Mtb for entry into macrophages remain to be fully understood. The mammalian cell entry (Mce) proteins play an essential role in facilitating the internalization of mycobacteria into mammalian cells. Here we characterized Mtb Mce3C as a new mycobacterial surface protein that could promote mycobacterial adhesion to and invasion of macrophages in an RGD motif-dependent manner...
November 10, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29118762/lc3-associated-phagocytosis-is-required-for-dendritic-cell-inflammatory-cytokine-response-to-gut-commensal-yeast-saccharomyces-cerevisiae
#3
Dimitra Lamprinaki, Gemma Beasy, Aleksandra Zhekova, Alexandra Wittmann, Steve James, Jo Dicks, Yoichiro Iwakura, Shinobu Saijo, Xiaomin Wang, Chung-Wai Chow, Ian Roberts, Tamas Korcsmaros, Ulrike Mayer, Thomas Wileman, Norihito Kawasaki
The human fungal microbiota known as mycobiota is increasingly recognized as a critical factor in human gut health and disease. Non-pathogenic commensal yeasts such as Saccharomyces cerevisiae promote homeostasis in the gut, whereas dysbiosis of the gut mycobiota is associated with inflammation. Glycan-binding receptors (lectins) are key host factors in host-mycobiota interaction in the gut. They are expressed on immune cells such as dendritic cells (DCs) and recognize fungal polysaccharides. This interaction is imperative to mount appropriate immune responses for immune homeostasis in the gut as well as clearance of fungal pathogens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29108825/targeting-interferons-and-their-pathways-in-systemic-lupus-erythematosus
#4
REVIEW
François Chasset, Laurent Arnaud
Significant advances in the understanding of the molecular basis of innate immunity have led to the identification of interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of Systemic Lupus Erythematosus. Therefore, targeting of IFNs and of their downstream pathways has emerged as important developments for novel drug research in SLE. Based on this, several specific interferon blocking strategies using anti-IFN-α antibodies, anti-type I interferon receptor antibodies, Interferon-α-kinoid, or anti-IFN-γ antibodies have all been assessed in recent clinical trials...
November 4, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29104084/orthopaedic-implant-materials-drive-m1-macrophage-polarization-in-a-spleen-tyrosine-kinase-and-mitogen-activated-protein-kinase-dependent-manner
#5
Olwyn R Mahon, Sarah O'Hanlon, Clare C Cunningham, Geraldine M McCarthy, Christopher Hobbs, Valeria Nicolosi, Daniel J Kelly, Aisling Dunne
Total joint replacements (TJR) are costly procedures required to relieve pain and restore function in patients suffering from end-stage arthritis. Despite great progress in the development and durability of TJRs, the generation of prosthesis-associated wear particles over time leads to an inflammatory cascade which culminates in periprosthetic osteolysis. Studies suggest that wear particles drive the polarization/differentiation of immature macrophages towards a pro-inflammatory M1 phenotype rather than an anti-inflammatory M2 phenotype associated with normal bone and wound healing...
November 2, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29091884/advances-in-chronic-lymphocytic-leukemia-pharmacotherapy
#6
REVIEW
Lorena Caixeta Gomes, Aline Lúcia Menezes Ferrão, Fernanda Cristina Gontijo Evangelista, Tâmara Dauare de Almeida, Rayson Carvalho Barbosa, Maria das Graças Carvalho, Adriano de Paula Sabino
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease that affects B lymphocytes in most cases. Leukemic lymphocytes have prolonged longevity, defined by resistance to apoptosis. These cells can accumulate in peripheral blood, bone marrow, and solid lymphoid organs. CLL may be indolent or aggressive and has a range of prognostic factors such as expression of CD38 and ZAP-70, immunophenotypic and cytogenetic changes, imbalanced apoptosis proteins, and others. Although CLL has a low mortality rate, this disease is generally not considered curable until today...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29056373/jte-852-a-novel-spleen-tyrosine-kinase-inhibitor-blocks-immunoglobulin-g-mediated-cellular-responses-and-autoimmune-reactions-in-vivo
#7
Toshinobu Kato, Takeshi Ohta, Hidenori Iwasaki, Hatsue Kobayashi, Akira Matsuo, Takahiro Hata, Mutsuyoshi Matsushita
AIMS: Immune and inflammatory responses mediated by immunoglobulin (Ig) G are largely responsible for the pathogenesis of autoimmune diseases. Spleen tyrosine kinase (Syk) plays a pivotal role in the IgG-mediated responses; therefore, Syk has emerged as a new therapeutic target for the treatment of autoimmune diseases. In this study, we investigated the inhibitory actions of JTE-852, a novel Syk inhibitor, on IgG-mediated cellular responses and autoimmune reactions in vivo. MAIN METHODS: We examined mediator secretion from human monocytes...
October 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/29052597/syk-expression-in-monomorphic-epitheliotropic-intestinal-t-cell-lymphoma
#8
Grit Mutzbauer, Katja Maurus, Clara Buszello, Jordan Pischimarov, Sabine Roth, Andreas Rosenwald, Andreas Chott, Eva Geissinger
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as type II enteropathy associated T-cell lymphoma (type II EATL), is a rare, aggressive primary intestinal T-cell lymphoma with a poor prognosis and an incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases of EATL, formerly known as type I EATL, and comparatively investigated the T-cell receptor (TCR) itself and associated signaling molecules using immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28967793/fostamatinib-for-persistent-chronic-adult-immune-thrombocytopenia
#9
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/28957395/high-mrna-expression-of-splice-variant-syk-short-correlates-with-hepatic-disease-progression-in-chemonaive-lymph-node-negative-colon-cancer-patients
#10
MULTICENTER STUDY
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/28951258/ibrutinib-suppresses-alloantibody-responses-in-a-mouse-model-of-allosensitization
#11
Irene Kim, Gordon Wu, Ning-Ning Chai, Andrew S Klein, Stanley Jordan
BACKGROUND: Ibrutinib is a Bruton's tyrosine Kinase (BTK) antagonist that inhibits B cell receptor (BCR) signaling. Complete BTK deficiency is associated with absence of B-cells. Ibrutinb is currently approved by FDA for treatment of B-cell malignancies, including Waldenström macroglobulinaemia. We recently carried out studies to determine if ibrutinib could modify alloantibody responses. MATERIALS AND METHODS: A mouse model of allogenic sensitization using a C57BL/6 mouse as the recipient of a skin allograft from an HLA-A2 transgenic mouse was utilized to examine the effects of ibrutinib on alloantibody responses and B cell effector functions...
September 23, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28950886/hm71224-a-selective-bruton-s-tyrosine-kinase-inhibitor-attenuates-the-development-of-murine-lupus
#12
Yu-Yon Kim, Ki Tae Park, Sun Young Jang, Kyu Hang Lee, Joo-Yun Byun, Kwee Hyun Suh, Young-Mi Lee, Young Hoon Kim, Kwang Woo Hwang
BACKGROUND: Systemic lupus erythematosus (SLE) is associated with B cell hyperactivity, and lupus nephritis (LN), in particular, is promoted by the production of autoantibodies and immune complex deposition. Bruton's tyrosine kinase (BTK) plays critical roles in B cell receptor-related and Fc receptor-related signaling. We aimed to investigate the impact of therapeutic intervention with HM71224 (LY3337641), a selective BTK inhibitor, on the development of murine SLE-like disease features...
September 26, 2017: Arthritis Research & Therapy
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
#13
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/28942884/overexpression-of-il-38-protein-in-anticancer-drug-induced-lung-injury-and-acute-exacerbation-of-idiopathic-pulmonary-fibrosis
#14
Masaki Tominaga, Masaki Okamoto, Tomotaka Kawayama, Masanobu Matsuoka, Shinjiro Kaieda, Yuki Sakazaki, Takashi Kinoshita, Daisuke Mori, Akira Inoue, Tomoaki Hoshino
BACKGROUND: Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. METHODS: To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5)...
September 2017: Respiratory Investigation
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 Fuhr, 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...
December 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28881711/characterization-of-midostaurin-as-a-dual-inhibitor-of-flt3-and-syk-and-potentiation-of-flt3-inhibition-against-flt3-itd-driven-leukemia-harboring-activated-syk-kinase
#16
Ellen L Weisberg, Alexandre Puissant, Richard Stone, Martin Sattler, Sara J Buhrlage, Jing Yang, Paul W Manley, Chengcheng Meng, Michael Buonopane, John F Daley, Suzan Lazo, Renee Wright, David M Weinstock, Amanda L Christie, Kimberly Stegmaier, James D Griffin
Oncogenic FLT3 kinase is a clinically validated target in acute myeloid leukemia (AML), and both multi-targeted and selective FLT3 inhibitors have been developed. Spleen tyrosine kinase (SYK) has been shown to be activated and increased in FLT3-ITD-positive AML patients, and has further been shown to be critical for transformation and maintenance of the leukemic clone in these patients. Further, over-expression of constitutively activated SYK causes resistance to highly selective FLT3 tyrosine kinase inhibitors (TKI)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878675/inhibition-of-collagen-induced-platelet-aggregation-by-the-secobutanolide-secolincomolide-a-from-lindera-obtusiloba-blume
#17
Sang-Hyuk Jung, Joo-Hui Han, Hyun-Soo Park, Jung-Jin Lee, Seo Young Yang, Young Ho Kim, Kyung-Sun Heo, Chang-Seon Myung
Atherothrombosis is one of the main underlying cause of cardiovascular diseases. In addition to treating atherothrombosis with antithrombotic agents, there is growing interest in the role of natural food products and biologically active ingredients for the prevention and treatment of cardiovascular diseases. This study aimed to investigate the effect of secolincomolide A (3) isolated from Lindera obtusiloba Blume on platelet activity and identify possible signaling pathways. In our study, the antiplatelet activities of 3 were measured by collagen-induced platelet aggregation and serotonin secretion in freshly isolated rabbit platelets...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28877763/alzheimer-s-disease-pathological-lesions-activate-the-spleen-tyrosine-kinase
#18
Jonas Elias Schweig, Hailan Yao, David Beaulieu-Abdelahad, Ghania Ait-Ghezala, Benoit Mouzon, Fiona Crawford, Michael Mullan, Daniel Paris
The pathology of Alzheimer's disease (AD) is characterized by dystrophic neurites (DNs) surrounding extracellular Aβ-plaques, microgliosis, astrogliosis, intraneuronal tau hyperphosphorylation and aggregation. We have previously shown that inhibition of the spleen tyrosine kinase (Syk) lowers Aβ production and tau hyperphosphorylation in vitro and in vivo. Here, we demonstrate that Aβ-overexpressing Tg PS1/APPsw, Tg APPsw mice, and tau overexpressing Tg Tau P301S mice exhibit a pathological activation of Syk compared to wild-type littermates...
September 6, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28869869/syk-protects-cardiocytes-against-anoxia-and-hypoglycemia-induced-injury-in-ischemic-heart-failure
#19
Guotian Yin, Xiuli Yang, Qiong Li, Zhikun Guo
Spleen tyrosine kinase (SYK), a non-receptor protein tyrosine kinase, is reported to be related to cell survival after A/H (anoxia/hypoglycemia) insult. However, the role of SYK in cardiocyte survival under A/H injury remains unclear. In this study, we aimed to gain insight into the role and molecular mechanism of SYK in cardiocytes exposed to A/H stress. The mRNA and protein expressions of SYK in H9c2 cardiocytes exposed to A/H injury, separately detected by real-time quantitative PCR and Western blot, were both robustly up-regulated...
November 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28857181/simultaneous-induction-of-hsp70-expression-and-degranulation-in-ige-ag-stimulated-or-extracellular-hsp70-stimulated-mast-cells-129-200
#20
Xian Li, Shiro Kanegasaki, Fansi Jin, Yifeng Deng, Jae-Ryong Kim, Hyeun Wook Chang, Tomoko Tsuchiya
BACKGROUND: In mast cells, induction of HSP70 expression during antigen stimulation has not been reported. METHODS: Mouse bone marrow derived mast cells (BMMC) were stimulated with IgE/Ag or HSP70. Induction of HSP70 expression, and signaling protein phosphorylation, were evaluated by immunoblotting. RESULTS: HSP70 expression is induced in BMMC at an early stage of IgE/Ag-dependent stimulation, some of which is released from the cells in a granule-associated form...
August 30, 2017: Allergy
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