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Syk cell expression

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https://www.readbyqxmd.com/read/28217127/cell-intrinsic-galectin-3-attenuates-neutrophil-ros-dependent-killing-of-candida-by-modulating-cr3-downstream-syk-activation
#1
Sheng-Yang Wu, Juin-Hua Huang, Wen-Yu Chen, Yi-Chen Chan, Chun-Hung Lin, Yee-Chun Chen, Fu-Tong Liu, Betty A Wu-Hsieh
Invasive candidiasis is a leading cause of nosocomial bloodstream infection. Neutrophils are the important effector cells in host resistance to candidiasis. To investigate the modulation of neutrophil fungicidal function will advance our knowledge on the control of candidiasis. While recombinant galectin-3 enhances neutrophil phagocytosis of Candida, we found that intracellular galectin-3 downregulates neutrophil fungicidal functions. Co-immunoprecipitation and immunofluorescence staining reveal that cytosolic gal3 physically interacts with Syk in neutrophils after Candida stimulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209719/adaptive-nk-cells-can-persist-in-patients-with-gata2-mutation-depleted-of-stem-and-progenitor-cells
#2
Heinrich Schlums, Moonjung Jung, Hongya Han, Jakob Theorell, Venetia Bigley, Samuel C C Chiang, David S J Allan, Jan K Davidson-Moncada, Rachel E Dickinson, Tim D Holmes, Amy P Hsu, Danielle Townsley, Thomas Winkler, Weixin Wang, Pål Aukrust, Ingvild Nordøy, Katherine R Calvo, Steve M Holland, Matthew Collin, Cynthia E Dunbar, Yenan T Bryceson
Heterozygous GATA2 mutation is associated with immunodeficiency, lymphedema, and myelodysplastic syndrome. Disease presentation is variable, often coinciding with loss of circulating dendritic cells, monocytes, B cells, and NK cells. Nonetheless, in a proportion of patients carrying GATA2 mutation, NK cells persist. We found that peripheral blood NK cells in symptomatic patients uniformly lacked expression of the transcription factor PLZF, as well as expression of intracellular signaling proteins FcϵRγ, SYK, and EAT-2 in a variegated manner...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28202529/aberrant-syk-kinase-signaling-is-essential-for-tumorigenesis-induced-by-tsc2-inactivation
#3
Ye Cui, Wendy K Steagall, Anthony Lamattina, Gustavo Pacheco-Rodriguez, Mario Stylianou, Pranav Kidambi, Benjamin Stump, Fernanda Golzarri, Ivan O Rosas, Carmen Priolo, Elizabeth P Henske, Joel Moss, Souheil El-Chemaly
Somatic or germline mutations in the tuberous sclerosis complex (TSC) tumor suppressor genes are associated closely with the pathogenesis of lymphangioleiomyomatosis (LAM), a rare and progressive neoplastic disease that predominantly affects women in their childbearing years. Serum levels of the lymphangiogeneic growth factor VEGF-D are elevated significantly in LAM. However, there are gaps in knowledge regarding VEGF-D dysregulation and its cellular origin in LAM. Here we show that increased expression and activation of the tyrosine kinase Syk in TSC2-deficient cells and pulmonary nodules from LAM patients contributes to tumor growth...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28178664/identification-of-distinct-molecular-subtypes-of-uterine-carcinosarcoma
#4
Yang An, Haojie Wang, Jingyao Jie, Yitai Tang, Weijuan Zhang, Shaoping Ji, Xiangqian Guo
Uterine carcinosarcoma (UCS) is a rare but lethal neoplasm with high metastasis and recurrence rate, and to date, no molecular classification of UCS has been defined to achieve targeted therapies. In this study, we identified two distinct molecular subtypes of UCS with distinct gene expression patterns and clinicopathologic characteristics. Subtype I UCS recapitulates low-grade UCS, in contrast subtype II UCS represents high-grade UCS with higher tumor invasion rate and tumor weight. Interestingly, subtype I UCS is characterized by cell adhesion and apoptosis pathways, whereas genes over-expressed in subtype II UCS are more involved in myogenesis/muscle development...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28173838/osteoarthritis-associated-basic-calcium-phosphate-crystals-activate-membrane-proximal-kinases-in-human-innate-immune-cells
#5
Emma M Corr, Clare C Cunningham, Laura Helbert, Geraldine M McCarthy, Aisling Dunne
BACKGROUND: Osteoarthritis (OA) is a chronic debilitating joint disorder of particularly high prevalence in the elderly population. Intra-articular basic calcium phosphate (BCP) crystals are present in the majority of OA joints and are associated with severe degeneration. They are known to activate macrophages, synovial fibroblasts, and articular chondrocytes, resulting in increased cell proliferation and the production of pro-inflammatory cytokines and matrix metalloproteases (MMPs)...
February 7, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28167474/regulatory-effect-of-caspase-11-on-interleukin-1%C3%AE-in-the-fungal-keratitis
#6
Keke Zhu, Hongmei Mu, Baimu Pi
Caused by fungus, fungal keratitis is a kind of infections corneal disease with high rate of blindness, which patients are mainly farmers in developing countries. Interleukin, as important proinflammatory cytokines, involve in immune defense process against fungal infection of cornea. The expression of interleukin in the pathogenesis of fungal keratitis, especially the main source of its cells, is not clear and the cell signaling pathways which regulate the synthesis and modification of interleukin is still unknown...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28154084/lymphocyte-activation-gene-3-a-novel-therapeutic-target-in-chronic-lymphocytic-leukemia
#7
Mika Shapiro, Yair Herishanu, Ben-Zion Katz, Nili Dezorella, Clare Sun, Sigi Kay, Aaron Polliack, Irit Avivi, Adrian Wiestner, Chava Perry
A novel therapeutic approach in cancer, attempting to stimulate host anti-tumor immunity, involves blocking of immune checkpoints. LAG3 is an immune checkpoint receptor expressed on activated/exhausted T-cells. When engaged by MHC class II molecules, LAG3 negatively regulates T-cell function thereby contributing to tumor escape. Intriguingly, a soluble LAG3 variant activates both immune and malignant MHC class II-presenting cells. In this study, we examined the role of LAG3 in the pathogenesis of chronic lymphocytic leukemia, an MHC class II-presenting malignancy, and show that chronic lymphocytic leukemia cells express and secrete LAG3...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28131718/spleen-tyrosine-kinase-mediates-the-actions-of-epo-and-gm-csf-and-coordinates-with-tgf-%C3%AE-in-erythropoiesis
#8
Hua-Ching Chang, Duen-Yi Huang, Mai-Szu Wu, Ching-Liang Chu, Shiang-Jong Tzeng, Wan-Wan Lin
Erythropoietin (EPO) and GM-CSF are involved in erythropoiesis, while TGF-β inhibits proliferation but potentiates differentiation of erythroblasts. Since Syk inhibitor may induce anemia side effect in clinic, here we investigated the role of Syk in the biological actions of EPO and GM-CSF in erythropoiesis. In human erythroleukemia cell line TF-1, Syk inhibitor R406 exerts an enhancement effect with TGF-β to decrease cell viability, either in the absence or presence of EPO or GM-CSF. Such effect of R406 results from the reduced cell cycle progression and increased cell apoptosis...
January 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28130153/the-role-of-alg13-n-acetylglucosaminyl-transferase-in-the-expression-of-pathogenic-features-of-candida-albicans
#9
Monika Niewiadomska, Anna Janik, Urszula Perlińska-Lenart, Sebastian Piłsyk, Grażyna Palamarczyk, Joanna S Kruszewska
BACKGROUND: The pathogenic potential of Candida albicans depends on adhesion to the host cells mediated by highly glycosylated adhesins, hyphae formation and growth of biofilm. These factors require effective N-glycosylation of proteins. Here, we present consequences of up- and down-regulation of the newly identified ALG13 gene encoding N-acetylglucosaminyl transferase, a potential member of the Alg7p/Alg13p/Alg14p complex catalyzing the first two initial reactions in the N-glycosylation process...
January 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28111009/glomerular-common-gamma-chain-confers-b-and-t-cell-independent-protection-against-glomerulonephritis
#10
Yosu Luque, Dominique Cathelin, Sophie Vandermeersch, Xiaoli Xu, Julie Sohier, Sandrine Placier, Yi-Chun Xu-Dubois, Kevin Louis, Alexandre Hertig, Jean-Christophe Bories, Florence Vasseur, Fabien Campagne, James P Di Santo, Christian Vosshenrich, Eric Rondeau, Laurent Mesnard
Crescentic glomerulonephritis is a life-threatening renal disease that has been extensively studied by the experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) model. Although T cells have a significant role in this model, athymic/nude mice and rats still develop severe renal disease. Here we further explored the contribution of intrinsic renal cells in the development of T-cell-independent GN lesions. Anti-GBM-GN was induced in three strains of immune-deficient mice (Rag2(-/-), Rag2(-/-)Il2rg(-/-), and Rag2(-/-)Il2rb(-/-)) that are devoid of either T/B cells or T/B/NK cells...
January 19, 2017: Kidney International
https://www.readbyqxmd.com/read/28107345/syk-regulates-neutrophilic-airway-hyper-responsiveness-in-a-chronic-mouse-model-of-allergic-airways-inflammation
#11
Sepehr Salehi, Xiaomin Wang, Stephen Juvet, Jeremy A Scott, Chung-Wai Chow
BACKGROUND: Asthma is a chronic inflammatory disease characterized by airways hyper-responsiveness (AHR), reversible airway obstruction, and airway inflammation and remodeling. We previously showed that Syk modulates methacholine-induced airways contractility in naïve mice and in mice with allergic airways inflammation. We hypothesize that Syk plays a role in the pathogenesis of AHR; this was evaluated in a chronic 8-week mouse model of house dust mite (HDM)-induced allergic airways inflammation...
2017: PloS One
https://www.readbyqxmd.com/read/28089901/over-expression-of-proteins-that-alter-the-intracellular-signaling-pathways-in-the-cytoplasm-of-the-liver-cells-forming-mallory-denk-bodies
#12
N Afifiyan, B Tillman, B A French, M Masouminia, S Samadzadeh, S W French
In this study, liver biopsy sections fixed in formalin and embedded in paraffin (FFPE) from patients with alcoholic hepatitis (AH) were used. The results showed that the expression of the SYK protein was up regulated by RNA-seq and real time PCR analyses in the alcoholic hepatitis patients compared to controls. The results were supported by using the IHC fluorescent antibody staining intensity morphometric quantitation. Morphometric quantification of fluorescent intensity measurement showed a two fold increase in SYK protein in the cytoplasm of the cells forming MDBs compared to surrounding normal hepatocytes...
February 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28064214/hsp90-promotes-burkitt-lymphoma-cell-survival-by-maintaining-tonic-b-cell-receptor-signaling
#13
Roland Walter, Kuan-Ting Pan, Carmen Doebele, Federico Comoglio, Katarzyna Tomska, Hanibal Bohnenberger, Ryan M Young, Laura Jacobs, Ulrich Keller, Halvard Bönig, Michael Engelke, Andreas Rosenwald, Henning Urlaub, Louis M Staudt, Hubert Serve, Thorsten Zenz, Thomas Oellerich
Burkitt lymphoma (BL) is an aggressive B cell neoplasm that is currently treated by intensive chemotherapy in combination with anti-CD20 antibodies. Due to their toxicity, current treatment regimens are often not suitable for elderly patients or for patients in developing countries where BL is endemic. Targeted therapies for BL are therefore needed. In this study, we performed a compound screen in 17 BL cell lines to identify small molecule inhibitors affecting cell survival. We found that inhibitors of heat shock protein 90 (HSP90) induced apoptosis in BL cells in vitro at concentrations that did not affect normal B cells...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28054556/phosphorylation-impact-on-spleen-tyrosine-kinase-conformation-by-surface-enhanced-raman-spectroscopy
#14
Maximilien Cottat, Ryohei Yasukuni, Yo Homma, Nathalie Lidgi-Guigui, Nadine Varin-Blank, Marc Lamy de la Chapelle, Christine Le Roy
Spleen Tyrosine Kinase (Syk) plays a crucial role in immune cell signalling and its altered expression or activation are involved in several cancers. Syk activity relies on its phosphorylation status and its multiple phosphorylation sites predict several Syk conformations. In this report, we characterized Syk structural changes according to its phosphorylation/activation status by Surface Enhanced Raman Spectroscopy (SERS). Unphosphorylated/inactive and phosphorylated/active Syk forms were produced into two expression systems with different phosphorylation capability...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28017324/the-pattern-recognition-receptor-mincle-is-essential-for-maintaining-the-m1-macrophage-phenotype-in-acute-renal-inflammation
#15
Lin L Lv, Patrick Ming-Kuen Tang, Chun J Li, Yong K You, Jinhong Li, Xiao-Ru Huang, Jun Ni, Min Feng, Bi C Liu, Hui-Yao Lan
Mincle (macrophage-inducible C-type lectin, Clec4e) is a transmembrane pattern recognition receptor involving the innate immunity, but its role in kidney disease is still unexplored. In the obstructed kidney of the unilateral ureteral obstruction model of renal injury, Mincle was specifically detected in the infiltrating M1 macrophages (CD68(+)iNOS(+) cells) on day one but was rapidly reduced following reduction of M1 macrophages during the progression of kidney injury. Interestingly, Mincle-expressing macrophages were progressively increased in the cisplatin-induced acute kidney injury model, where iNOS expression was detected in the CD68(+) cells following Mincle induction...
December 22, 2016: Kidney International
https://www.readbyqxmd.com/read/28011996/the-kinase-inhibitors-r406-and-gs-9973-impair-t-cell-functions-and-macrophage-mediated-anti-tumor-activity-of-rituximab-in-chronic-lymphocytic-leukemia-patients
#16
Ana Colado, María Belén Almejún, Enrique Podaza, Denise Risnik, Carmen Stanganelli, Esteban Enrique Elías, Patricia Dos Santos, Irma Slavutsky, Horacio Fernández Grecco, María Cabrejo, Raimundo Fernando Bezares, Mirta Giordano, Romina Gamberale, Mercedes Borge
Small molecules targeting kinases involved in B cell receptor signaling are showing encouraging clinical activity in chronic lymphocytic leukemia (CLL) patients. Fostamatinib (R406) and entospletinib (GS-9973) are ATP-competitive inhibitors designed to target spleen tyrosine kinase (Syk) that have shown clinical activity with acceptable toxicity in trials with CLL patients. Preclinical studies with these inhibitors in CLL have focused on their effect in patient-derived leukemic B cells. In this work we show that clinically relevant doses of R406 and GS-9973 impaired the activation and proliferation of T cells from CLL patients...
December 23, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28011673/distinct-patterns-of-b-cell-receptor-signaling-in-non-hodgkins-lymphomas-identified-by-single-cell-profiling
#17
June H Myklebust, Joshua Brody, Holbrook E Kohrt, Arne Kolstad, Debra K Czerwinski, Sébastien Wälchli, Michael R Green, Gunhild Trøen, Knut Liestøl, Klaus Beiske, Roch Houot, Jan Delabie, Ash A Alizadeh, Jonathan M Irish, Ronald Levy
Kinases downstream of B-cell antigen receptor (BCR) represent attractive targets for therapy in non-Hodgkins' lymphoma (NHL). As clinical responses vary, improved knowledge regarding activation and regulation of BCR signaling in individual patients is needed. Here, using phospho-specific flow cytometry to obtain signaling profiles of malignant B cells from 95 patients representing 4 types of NHL, revealed a striking contrast between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) tumors. Lymphoma cells from diffuse large B-cell lymphoma patients had high basal phosphorylation levels of most of the measured signaling nodes, whereas follicular lymphoma cells represented the opposite pattern with no or very low basal levels...
December 23, 2016: Blood
https://www.readbyqxmd.com/read/27998003/vitamin-d-contributes-to-mast-cell-stabilization
#18
Zhi-Qiang Liu, Xiao-Xi Li, Shu-Qi Qiu, Yong Yu, Mao-Gang Li, Li-Tao Yang, Lin-Jing Li, Shuai Wang, Peng-Yuan Zheng, Zhi-Gang Liu, Ping-Chang Yang
BACKGROUND AND AIMS: Mast cells are the major effector cells in allergic disorders and many other informatory disorders. The mechanism of mast cell stabilization is not fully understood. Cumulative reports indicate that vitamin D (VitD) contributes to the homeostasis in the body. This study tests a hypothesis that VitD is required in the maintenance of the stability of mast cells. METHODS: The stability of mast cell lines, HMC1 cells, RBL-2H3 cells, p815 cells and mouse bone marrow-derived mast cells (BMMC) was tested in the presence or absence of VitD3...
December 20, 2016: Allergy
https://www.readbyqxmd.com/read/27974454/the-systemic-lupus-erythematosus-associated-single-nucleotide-polymorphism-rs1143678-in-integrin-%C3%AE-m-cytoplasmic-tail-generates-a-14-3-3%C3%AE-binding-site-that-is-proinflammatory
#19
Li-Teng Ong, Hui-Foon Tan, Chen Feng, Jing Qu, Shuzk-Cheng Loh, Surajit Bhattacharyya, Suet-Mien Tan
The leukocyte integrin αMβ2 (CR3 or Mac-1) has both proinflammatory and immune regulatory functions. Genome-wide association studies have identified several ITGAM (αM subunit) single nucleotide polymorphisms that are associated with systemic lupus erythematosus. The single nucleotide polymorphism rs1143678 substitutes Pro(1146) for Ser in the integrin αM cytoplasmic tail. A detailed functional characterization of this substitution is lacking. Using transfected human cell lines, reconstituted mouse bone marrow neutrophils, and bone marrow-derived macrophages (BMDMs), we showed that P1146S (PS) substitution promoted integrin αMβ2-mediated adhesion, spreading, and migration of cells on iC3b and fibrinogen...
December 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27906453/spleen-tyrosine-kinase-inhibition-blocks-airway-constriction-and-protects-from-th2-induced-airway-inflammation-and-remodeling
#20
C Tabeling, J Herbert, A C Hocke, D J Lamb, S L Wollin, K J Erb, E Boiarina, H Movassagh, J Scheffel, J M Doehn, S Hippenstiel, M Maurer, A S Gounni, W M Kuebler, N Suttorp, M Witzenrath
BACKGROUND: Spleen tyrosine kinase (Syk) is an intracellular nonreceptor tyrosine kinase, which has been implicated as central immune modulator promoting allergic airway inflammation. Syk inhibition has been proposed as a new therapeutic approach in asthma. However, the direct effects of Syk inhibition on airway constriction independent of allergen sensitization remain elusive. METHODS: Spectral confocal microscopy of human and murine lung tissue was performed to localize Syk expression...
December 1, 2016: Allergy
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