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Spleen tyrosine kinase

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https://www.readbyqxmd.com/read/29342970/the-possible-importance-of-%C3%AE-3-integrins-for-leukemogenesis-and-chemoresistance-in-acute-myeloid-leukemia
#1
REVIEW
Silje Johansen, Annette K Brenner, Sushma Bartaula-Brevik, Håkon Reikvam, Øystein Bruserud
Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the immature leukemia cells communicate with neighboring cells through constitutive cytokine release and through their cell surface adhesion molecules. The primary AML cells express various integrins. These heterodimeric molecules containing an α and a β chain are cell surface molecules that bind extracellular matrix molecules, cell surface molecules and soluble mediators. The β3 integrin (ITGB3) chain can form heterodimers only with the two α chains αIIb and αV...
January 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29340070/a-novel-orally-available-syk-src-jak2-inhibitor-sklb-850-showed-potent-anti-tumor-activities-in-b-cell-lymphoma-bcl-models
#2
Nannan Zhang, Guo Zhang, Ning Liu, Wanting Lin, Sen Ji, Mingwu Zheng, Kai Chen, Xiao Liang, Guobo Li, Yu Ma, Jun Zhu, Ting Niu, Lin-Li Li, Jiong Li, Yu-Quan Wei, Sheng-Yong Yang
B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as potential targets for the treatment of BCL. We have recently developed a multikinase inhibitor, SKLB-850, which potently inhibits Syk, Src, and JAK2. The aim of this study is to investigate the anti-BCL activities and mechanisms of action of SKLB-850 both in vitro and in vivo. Our results showed that SKLB-850 significantly inhibited BCL cell proliferation, and induced apoptosis of BCL cells...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29336019/computerized-planimetry-to-assess-clinical-responsiveness-in-a-phase-ii-randomized-trial-of-topical-r333-for-discoid-lupus-erythematosus
#3
J K Presto, L G Okon, R Feng, D J Wallace, R Furie, D Fiorentino, V P Werth
BACKGROUND: R333 is a topical janus kinase and spleen tyrosine kinase inhibitor being evaluated for discoid lupus erythematosus (DLE) treatment. There is no validated measure to assess area of active DLE lesions. OBJECTIVES: To evaluate R333 efficacy and assess a technique to measure responsiveness. METHODS: 54 DLE patients were randomized in a double blind design to R333 or placebo. The primary endpoint was the proportion of patients achieving ≥50% decrease in erythema and scale based on lesional CLASI for all treated lesions at week 4...
January 16, 2018: British Journal of Dermatology
https://www.readbyqxmd.com/read/29328440/methanol-extract-of-guettarda-speciosa-linn-inhibits-the-production-of-inflammatory-mediators-through-the-inactivation-of-syk-and-jnk-in-macrophages
#4
Hien Thi Thu Le, Young-Chang Cho, Sayeon Cho
Guettarda speciosa Linn. (G. speciosa, Rubiaceae) has been used as a traditional medicinal plant in Asia for the treatment of various inflammatory conditions, including cough, fever and maternal postpartum infection. However, the mechanisms underlying the anti‑inflammatory action of G. speciosa extracts have remained elusive. In the present study, the anti‑inflammatory effects of the methanol extract of G. speciosa (MGS) were investigated in murine macrophages by measuring the production of inflammatory mediators and the underlying mechanisms of action by performing immunoblotting analysis of proteins that are potentially involved...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29296975/cell-surface-c-type-lectin-like-receptor-clec-1-dampens-dendritic-cell-activation-and-downstream-th17-responses
#5
Maria Dolores Lopez Robles, Annaick Pallier, Virginie Huchet, Laetitia Le Texier, Severine Remy, Cecile Braudeau, Laurence Delbos, Aurelie Moreau, Cedric Louvet, Carole Brosseau, Pierre-Joseph Royer, Antoine Magnan, Franck Halary, Regis Josien, Maria-Cristina Cuturi, Ignacio Anegon, Elise Chiffoleau
Dendritic cells (DCs) represent essential antigen-presenting cells that are critical for linking innate and adaptive immunity, and influencing T-cell responses. Among pattern recognition receptors, DCs express C-type lectin receptors triggered by both exogenous and endogenous ligands, therefore dictating pathogen response, and also shaping T-cell immunity. We previously described in rat, the expression of the orphan C-type lectin-like receptor-1 (CLEC-1) by DCs and demonstrated in vitro its inhibitory role in downstream T helper 17 (Th17) activation...
March 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29286114/cigarette-smoke-induced-egfr-activation-promotes-epithelial-mesenchymal-migration-of-human-retinal-pigment-epithelial-cells-through-regulation-of-the-fak-mediated-syk-src-pathway
#6
Ga Bin Park, Daejin Kim
Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is inevitable change of age‑related macular degeneration (AMD). Smoking is a major risk factor for the development of EMT in several diseases, including lung cancer. Cigarette smoke‑induced stress promotes the production of epidermal growth factor (EGF) in RPE cells. However, the underlying signaling pathways induced by aberrant EGF receptor (EGFR) expression in cigarette smoke-exposed RPE cells remain largely unknown. In the present study, the morphological transformation and production of EMT-associated cytokines were investigated to analyze the effect of smoking on the retina...
December 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29286055/midostaurin-for-the-treatment-of-adult-patients-with-newly-diagnosed-acute-myeloid-leukemia-that-is-flt3-mutation-positive
#7
J S Garcia, M E Percival
Midostaurin is a multitargeted tyrosine kinase inhibitor (TKI) that potently inhibits activated fms-related tyrosine kinase 3 (FLT3) in the nanomolar range and other kinases including platelet-derived growth factor receptors α (PDGFR- α) and β (PDGFR- β), cyclin-dependent kinase, proto-oncogene tyrosine-protein kinase Src, tyrosine-protein kinase Fgr, spleen tyrosine kinase (Syk), KIT proto-oncogene receptor tyrosine kinase and the major vascular endothelial growth factor receptor (VEGFR). Activating mutations in FLT3, which is one of the more common acute myeloid leukemia (AML) mutations, particularly those that result in an FLT3-ITD (internal tandem duplication) mutation, confer poor prognosis and represent a therapeutic target...
October 2017: Drugs of Today
https://www.readbyqxmd.com/read/29274344/calcium-phosphate-particles-stimulate-interleukin-1%C3%AE-release-from-human-vascular-smooth-muscle-cells-a-role-for-spleen-tyrosine-kinase-and-exosome-release
#8
Yana Dautova, Alexander N Kapustin, Kevin Pappert, Matthias Epple, Hanneke Okkenhaug, Simon J Cook, Catherine M Shanahan, Martin D Bootman, Diane Proudfoot
AIMS: Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs...
December 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29249894/spleen-tyrosine-kinase-inhibition-modulates-p53-activity
#9
Mohammad Althubiti
Spleen tyrosine kinase (SYK) is a cytoplasmic enzyme that promotes survival and proliferation of B cells. SYK inhibition has shown promising results in the treatment of arthritis and chronic lymphocytic leukemia (CLL). However, in other context, it has been shown that SYK overexpression in epithelial cancer cells induced senescence in p53-dependent mechanism, which underscored its antineoplastic activity in vitro. Here, we show that SYK was induced in response of DNA damage in parallel with p53 levels. In addition, using chemical inhibitors of SYK reduced p53 levels in HCT116 and HT1080 cell lines, which underlines the role of SYK inhibition on p53 activity...
2017: Journal of Cell Death
https://www.readbyqxmd.com/read/29241811/syk-and-src-targeted-anti-inflammatory-activity-of-aripiprazole-an-atypical-antipsychotic
#10
Sulgi Yoo, Mi-Yeon Kim, Jae Youl Cho
Aripiprazole (ARP) is a partial agonist of dopamine D2 receptors that is commonly prescribed to treat schizophrenia and bipolar disorder. The anti-inflammatory effect of ARP was recently documented in a few studies, but its molecular mechanisms have not been fully elucidated. In this study, peptidoglycan (PGN)-treated macrophages (RAW264.7 cells), reporter gene assay, an overexpression strategy, immunoprecipitation, and immunoblotting analysis were employed to clarify the anti-inflammatory mechanism of ARP...
December 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29236491/short-chain-fatty-acids-suppress-inflammatory-reactions-in-caco-2-cells-and-mouse-colons
#11
Tran Van Hung, Takuya Suzuki
Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, play an important role in the maintenance of intestinal homeostasis. In the present study, anti-inflammatory effects of SCFAs were examined in human intestinal Caco-2 cells and mouse colonic cultures. Stimulation of Caco-2 cells with tumor necrosis factor (TNF)-α induced interleukin (IL)-8 (TNF-α, 17.1 ± 7.2 vs Control, 1.00 ± 0.26, P < 0.01) and IL-6 expression (TNF-α, 21.7 ± 10.0 vs Control, 1.00 ± 0.28, P < 0.01) through the activation of nuclear factor κB p65, spleen tyrosine kinase, and mitogen-activated protein kinase pathways...
December 26, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29235464/syk-kinase-mediates-brown-fat-differentiation-and-activation
#12
Marko Knoll, Sally Winther, Anirudh Natarajan, Huan Yang, Mengxi Jiang, Prathapan Thiru, Aliakbar Shahsafaei, Tony E Chavarria, Dudley W Lamming, Lei Sun, Jacob B Hansen, Harvey F Lodish
Brown adipose tissue (BAT) metabolism influences glucose homeostasis and metabolic health in mice and humans. Sympathetic stimulation of β-adrenergic receptors in response to cold induces proliferation, differentiation, and UCP1 expression in pre-adipocytes and mature brown adipocytes. Here we show that spleen tyrosine kinase (SYK) is upregulated during brown adipocyte differentiation and activated by β-adrenergic stimulation. Deletion or inhibition of SYK, a kinase known for its essential roles in the immune system, blocks brown and white pre-adipocyte proliferation and differentiation in vitro, and results in diminished expression of Ucp1 and other genes regulating brown adipocyte function in response to β-adrenergic stimulation...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29231998/phosphorylated-tyr142-%C3%AE-catenin-localizes-to-centrosomes-and-is-regulated-by-syk
#13
D Bhardwaj, M Náger, A Visa, M C Sallán, P J Coopman, C Cantí, J Herreros
β-catenin is a central component of adherent junctions and a key effector of canonical Wnt signalling, in which dephosphorylated Ser/Thr β-catenin regulates gene transcription. β-catenin phosphorylation at Tyr142 (PTyr142 β-catenin), which is induced by receptor and Src family Tyr kinases, represents a previously described β-catenin switch from adhesive to migratory roles. In addition to classical β-catenin roles, phosphorylated Ser/Thr β-catenin and total β-catenin were involved in centrosomal functions, including mitotic spindle formation and centrosome separation...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29202301/spleen-tyrosine-kinase-inhibition-ameliorates-airway-inflammation-through-modulation-of-nlrp3-inflammosome-and-th17-treg-axis
#14
Divyesh Patel, Sagar Gaikwad, Naveen Challagundla, Manish Nivsarkar, Reena Agrawal-Rajput
Repeated exposure to the fungal pathogen Aspergillus fumigates triggers spleen tyrosine kinase (SYK) signalling through dectin-1 activation, which is associated with deleterious airway inflammation. β-Glucan-induced dectin-1 signalling activates the NLRP3 inflammasome, which in turn rapidly produces IL-1β, a master regulator of inflammation. IL-1β expression results in Th17/Treg imbalance, pulmonary inflammation, and bystander tissue injury. This study reports that 3,4 methylenedioxy-β-nitrostyrene (MNS), a potent SYK inhibitor, markedly decreased the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines in vitro...
December 1, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29192558/spleen-tyrosine-kinase-inhibition-a-new-promising-approach-to-chronic-and-refractory-immune-thrombocytopenia
#15
Pasquale Niscola, Laura Scaramucci, Marco Giovannini
No abstract text is available yet for this article.
January 2018: Immunotherapy
https://www.readbyqxmd.com/read/29153923/macrophages-sensing-oxidized-damps-reprogram-their-metabolism-to-support-redox-homeostasis-and-inflammation-through-a-tlr2-syk-ceramide-dependent-mechanism
#16
Vlad Serbulea, Clint M Upchurch, Katelyn W Ahern, Gael Bories, Paxton Voigt, Dory E DeWeese, Akshaya K Meher, Thurl E Harris, Norbert Leitinger
OBJECTIVE: Macrophages control tissue homeostasis and inflammation by sensing and responding to environmental cues. However, the metabolic adaptation of macrophages to oxidative tissue damage and its translation into inflammatory mechanisms remains enigmatic. METHODS: Here we identify the critical regulatory pathways that are induced by endogenous oxidation-derived DAMPs (oxidized phospholipids, OxPL) in vitro, leading to formation of a unique redox-regulatory metabolic phenotype (Mox), which is strikingly different from conventional classical or alternative macrophage activation...
November 7, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29146750/trpm7-transient-receptor-potential-melastatin-like-7-channel-kinase-controls-calcium-responses-in-arterial-thrombosis-and-stroke-in-mice
#17
Sanjeev K Gotru, Wenchun Chen, Peter Kraft, Isabelle C Becker, Karen Wolf, Simon Stritt, Susanna Zierler, Heike M Hermanns, Deviyani Rao, Anne-Laure Perraud, Carsten Schmitz, René P Zahedi, Peter J Noy, Michael G Tomlinson, Thomas Dandekar, Masayuki Matsushita, Vladimir Chubanov, Thomas Gudermann, Guido Stoll, Bernhard Nieswandt, Attila Braun
OBJECTIVE: TRPM7 (transient receptor potential melastatin-like 7 channel) is a ubiquitously expressed bifunctional protein comprising a transient receptor potential channel segment linked to a cytosolic α-type serine/threonine protein kinase domain. TRPM7 forms a constitutively active Mg(2+) and Ca(2+) permeable channel, which regulates diverse cellular processes in both healthy and diseased conditions, but the physiological role of TRPM7 kinase remains largely unknown. APPROACH AND RESULTS: Here we show that point mutation in TRPM7 kinase domain deleting the kinase activity in mice (Trpm7(R/R) ) causes a marked signaling defect in platelets...
November 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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
#18
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/mycobacterium-tuberculosis-mce3c-promotes-mycobacteria-entry-into-macrophages-through-activation-of-%C3%AE-2-integrin-mediated-signalling-pathway
#19
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 internalisation 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 internalisation 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
#20
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
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