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syk AND the cell

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https://www.readbyqxmd.com/read/28634183/syk-inhibitors-interfere-with-erythrocyte-membrane-modification-during-p-falciparum-growth-and-suppress-parasite-egress
#1
Antonella Pantaleo, Kristina R Kesely, Maria Carmina Pau, Ioannis Tsamesidis, Evelin Schwarzer, Oleksii A Skorokhod, Huynh D Chien, Marta Ponzi, Lucia Bertuccini, Philip S Low, Francesco M Turrini
Band 3 (a.k.a. the anion exchanger, SLCA1, AE1) constitutes the major attachment site of the spectrin-based cytoskeleton to the erythrocyte's lipid bilayer and thereby contributes critically to the stability of the red cell membrane. During the intra-erythrocytic stage of Plasmodium falciparum's life cycle, band 3 becomes tyrosine phosphorylated in response to oxidative stress, leading to a decrease in its affinity for the spectrin/actin cytoskeleton and causing global membrane destabilization. Because this membrane weakening is hypothesized to facilitate parasite egress and the consequent dissemination of released merozoites throughout the bloodstream, we decided to explore which tyrosine kinase inhibitors might block the kinase-induced membrane destabilization...
June 20, 2017: Blood
https://www.readbyqxmd.com/read/28624575/intestinal-fungal-dysbiosis-associates-with-visceral-hypersensitivity-in-patients-with-irritable-bowel-syndrome-and-rats
#2
Sara Botschuijver, Guus Roeselers, Evgeni Levin, Daisy M Jonkers, Olaf Welting, Sigrid Em Heinsbroek, Heleen H de Weerd, Teun Boekhout, Matteo Fornai, Ad A Masclee, Frank H J Schuren, Wouter J de Jonge, Jurgen Seppen, Rene M van den Wijngaard
BACKGROUND & AIMS: Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity. METHODS: We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity)...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28614370/the-hemagglutinin-neuramidinase-protein-of-newcastle-disease-virus-upregulates-expression-of-the-trail-gene-in-murine-natural-killer-cells-through-the-activation-of-syk-and-nf-%C3%AE%C2%BAb
#3
Ying Liang, De-Zhi Song, Shuang Liang, Zeng-Feng Zhang, Ling-Xi Gao, Xiao-Hui Fan
Newcastle disease virus (NDV) is responsible for tumoricidal activity in vitro and in vivo. However, the mechanisms that lead to this activity are unclear. Natural killer cells are able to induce apoptosis of tumor cells through multiple pathways, including the tumor necrosis factor-related apoptosis-inducing ligand-death receptor pathway. We previously showed that exposure of NK and T cells to NDV resulted in enhanced tumoricidal activity that was mediated by upregulated expression of the TRAIL gene, via an interferon gamma -dependent pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28594748/inhibition-of-spleen-tyrosine-kinase-reduces-renal-allograft-injury-in-a-rat-model-of-acute-antibody-mediated-rejection-in-sensitized-recipients
#4
Sharmila Ramessur Chandran, Yingjie Han, Greg H Tesch, Julie Di Paolo, William R Mulley, John Kanellis, Frank Y Ma, David J Nikolic-Paterson
BACKGROUND: Organ transplantation into sensitized patients with preexisting donor-specific antibodies (DSA) is very challenging. Spleen tyrosine kinase (Syk) promotes leukocyte recruitment and activation via signalling through various cell surface receptors. We investigated whether a selective Syk inhibitor (GS-492429) could suppress antibody-mediated rejection (AMR) in a rat model of AMR in sensitized recipients. METHODS: Recipient Lewis rats (RT1) were immunized with donor (Dark Agouti, RT1) spleen cells (day -5)...
June 7, 2017: Transplantation
https://www.readbyqxmd.com/read/28536300/receptor-cooperation-in-b-cells
#5
John F Foley
TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor.
May 23, 2017: Science Signaling
https://www.readbyqxmd.com/read/28506889/nfam1-signaling-enhances-osteoclast-formation-and-bone-resorption-activity-in-paget-s-disease-of-bone
#6
Yuvaraj Sambandam, Kumaran Sundaram, Takamitsu Saigusa, Sundaravadivel Balasubramanian, Sakamuri V Reddy
Paget's disease of bone (PDB) is marked by the focal activity of abnormal osteoclasts (OCLs) with excess bone resorption. We previously detected measles virus nucleocapsid protein (MVNP) transcripts in OCLs from patients with PDB. Also, MVNP stimulates pagetic OCL formation in vitro and in vivo. However, the mechanism by which MVNP induces excess OCLs/bone resorption activity in PDB is unclear. Microarray analysis identified MVNP induction of NFAM1 (NFAT activating protein with ITAM motif 1) expression. Therefore, we hypothesize that MVNP induction of NFAM1 enhances OCL differentiation and bone resorption in PDB...
May 12, 2017: Bone
https://www.readbyqxmd.com/read/28500073/fc%C3%AE-riiia-signaling-modulates-endosomal-tlr-responses-in-human-cd4-t-cells
#7
Anil K Chauhan
Recognition of Ab-opsonized pathogens by immune cells triggers both TLR and Fc receptor signaling. Fc receptors endocytose modified nucleic acids bound to Abs and deliver them to endosomes, where they are recognized by nucleic acid-sensing TLRs (NA-TLRs). We show that in CD4(+) T cells, NA-TLRs, TLR3, TLR8, and TLR9 are upregulated by FcγRIIIa-pSyk cosignaling and localize with FcγRIIIa on the cell surface. TLR9 accumulates on the cell surface, where it recognizes CpG oligonucleotide 2006. Subcellular location of NA-TLRs is a key determinant in discriminating self versus viral nucleic acid...
June 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28495615/a-novel-function-of-tlr4-in-mediating-the-immunomodulatory-effect-of-benzanthrone-an-environmental-pollutant
#8
Prachi Tewari, Payal Mandal, Ruchi Roy, Somya Asthana, Premendra D Dwivedi, Mukul Das, Anurag Tripathi
Our prior studies have reported that Benzanthrone (BA) manifests inflammatory responses in the spleen of Balb/c mice. The present investigation was carried out to study the impact of BA on macrophages, which are the primary scavenger cells in the body that act as a connecting link between innate and adaptive immunity. Parenteral administration of BA (daily for one week) to mice resulted in enhanced levels of nitric oxide (NO) and overexpression of inflammatory markers (COX-2, MMP-9 and PGE-2) in macrophages; however the level of MHC class-I and MHC class-II receptors were down regulated...
July 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28494724/c-type-lectin-receptor-old-friend-and-new-player
#9
Hai Hou, Yahui Guo, Qing Chang, Tianming Luo, Xin Wu, Xueqiang Zhao
During the last two decades, C-type lectin receptors (CLRs) have been demonstrated to play key roles in initiating the host immune response upon fungal infection. It is well established that CLRs, such as Dectin-1, Dectin-2, Dectin-3 and Mincle, recognize the cell wall component from the infected microorganisms by using their carbohydrate recognition domain (CRD). Upon stimulation, CLRs induce multiple signal transduction cascades through their own immune-receptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM-containing adaptor proteins such as FcRγ, which then lead to the activation of nuclear factor kappa B (NF-kB) through Syk- and CARD9-dependent pathway...
May 9, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28490631/a-split-luciferase-complementation-real-time-reporting-assay-enables-monitoring-of-the-disease-associated-transmembrane-protein-trem2-in-live-cells
#10
Megan M Varnum, Kevin A Clayton, Asuka Yoshii-Kitahara, Grant Yonemoto, Lacin Koro, Seiko Ikezu, Tsuneya Ikezu
Triggering receptor expressed on myeloid cells 2 (TREM2) is a single transmembrane molecule uniquely expressed in microglia. TREM2 mutations are genetically linked to Nasu-Hakola disease and associated with multiple neurodegenerative disorders, including Alzheimer's disease (AD). TREM2 may regulate microglial inflammation and phagocytosis through coupling to the adaptor protein, TYRO protein tyrosine kinase binding protein (TYROBP). However, there is no functional system for monitoring this protein-protein interaction...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28484282/measuring-nanoscale-viscoelastic-parameters-of-cells-directly-from-afm-force-displacement-curves
#11
Yuri M Efremov, Wen-Horng Wang, Shana D Hardy, Robert L Geahlen, Arvind Raman
Force-displacement (F-Z) curves are the most commonly used Atomic Force Microscopy (AFM) mode to measure the local, nanoscale elastic properties of soft materials like living cells. Yet a theoretical framework has been lacking that allows the post-processing of F-Z data to extract their viscoelastic constitutive parameters. Here, we propose a new method to extract nanoscale viscoelastic properties of soft samples like living cells and hydrogels directly from conventional AFM F-Z experiments, thereby creating a common platform for the analysis of cell elastic and viscoelastic properties with arbitrary linear constitutive relations...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28479222/effects-of-a-spleen-tyrosine-kinase-inhibitor-on-progression-of-the-lupus-nephritis-in-mice
#12
Maki Kitai, Noboru Fukuda, Takahiro Ueno, Morito Endo, Takashi Maruyama, Masanori Abe, Kazuyoshi Okada, Masayoshi Soma, Koichi Matsumoto
The Fc receptors (FcR) have pivotal roles in the pathogenesis of the autoimmune glomerulonephritis. We therefore investigated the effects of a Syk inhibitor on the progression of lupus nephritis and SH3 domain binding protein 2 and p38MAP kinase signalings in mice. NZB/W F1 mice, a model of lupus nephritis, received a Syk inhibitor R406. Western blotting and immunohistochemistry revealed that R406 treatment significantly delayed the appearance of proteinuria, histologically improved their glomerulosclerosis and inhibited the increased the expression of MCP-1 and TGF-β1 mRNAs and the nephrin and podocin proteins in the kidney...
May 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28468967/high-syk-expression-drives-constitutive-activation-of-cd21-low-b-cells
#13
Baerbel Keller, Ina Stumpf, Valentina Strohmeier, Susanne Usadel, Els Verhoeyen, Hermann Eibel, Klaus Warnatz
Human CD21(low) B cells present with an activated phenotype and accumulate in distinct disorders connected with chronic immune stimulation. Signaling studies had revealed an increased basal phosphorylation of spleen tyrosine kinase (SYK) and phospholipase Cγ2. Additional BCR stimulation of these constitutively active cells, however, led to reduced activation of these signaling molecules and subsequently NF-κB and Ca(2+) activation. In this article, we demonstrate that high SYK expression is a common feature of CD21(low) B cells independent of the underlying disorder, and that this high expression is sufficient to drive constitutive phosphorylation of SYK and its immediate targets Bruton's tyrosine kinase and phospholipase Cγ2...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28462919/targeting-antigen-independent-proliferation-in-chronic-lymphocytic-leukemia-through-differential-kinase-inhibition
#14
E Slinger, R Thijssen, A P Kater, E Eldering
The clinical success of B cell receptor (BCR) signaling pathway inhibitors in chronic lymphocytic leukemia (CLL) is attributed to inhibition of adhesion in and migration towards the lymph node. Proliferation of CLL cells is restricted to this protective niche, but the underlying mechanism(s) is/are not known. Treatment with BCR pathway inhibitors results in rapid reductions of total clone size, while CLL cell survival is not affected, which points towards inhibition of proliferation. However, BCR stimulation does not induce proliferation of CLL in vitro, while triggering via TLR-, TNF- or cytokine- receptors does...
May 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28461777/js-iii-49-a-hydroquinone-derivative-exerts-anti-inflammatory-activity-by-targeting-akt-and-p38
#15
Young-Su Yi, Mi-Yeon Kim, Jae Youl Cho
Since previous studies have reported that hydroquinone (HQ) exerted immunosuppressive and anti-inflammatory activity, various HQ derivatives have been synthesized and their biological activities investigated. In this study, we explored the anti-inflammatory activity of JS-III-49, a novel HQ derivative, in macrophage-mediated inflammatory responses. JS-III-49 suppressed the production of the inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2) and down-regulated the mRNA expression of the inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-1b without cytotoxicity in LPS-stimulated RAW264...
May 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28460620/cx-4945-a-selective-inhibitor-of-casein-kinase-2-synergizes-with-b-cell-receptor-signaling-inhibitors-in-inducing-diffuse-large-b-cell-lymphoma-cell-death
#16
Elisa Mandato, Sara Canovas Nunes, Fortunato Zaffino, Alessandro Casellato, Paolo Macaccaro, Laura Quotti Tubi, Andrea Visentin, Livio Trentin, Gianpietro Semenzato, Francesco Piazza
BACKGROUND: Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and promotes a "non-oncogene addiction" phenotype. Whether this kinase regulates BCR signaling thus being a suitable pharmacological target in DLBCL is unknown. OBJECTIVE: To establish if CK2 controls DLBCL cell survival and the BCR signaling; to check if the combination of CK2 inhibitor CX-4945 and BCR blockers Ibrutinib and Fostamatinib is more effectively cytotoxic for DLBCL cells than the single agents; to survey the changes in signaling molecules downstream BCR upon CK2 inhibition...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28454101/mir-146a-negatively-regulates-dectin-1-induced-inflammatory-responses
#17
Leilei Du, Xu Chen, Zhimin Duan, Caixia Liu, Rong Zeng, Qing Chen, Min Li
Dectin-1 is the critical sensor for β-glucan from Candida which is the most common human fungal pathogen and cause superficial and system infection. MicroRNAs (miRNAs) play crucial roles in regulating innate immunity. However, the functional role of miRNAs in inflammatory response dependent on the activation of dectin-1 pathway has not been defined. In the present study, we found insoluble β-glucan from the cell wall of Candida albicans (CaIG) was able to increase the production of of IL-6 and TNFα through Dectin-1-Syk-NF-κB and p38MAPK pathway...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445193/a-pilot-randomized-trial-on-safety-and-efficacy-of-a-novel-topical-combined-inhibitor-of-janus-kinase-1-3-and-spleen-tyrosine-kinase-for-gvhd-associated-ocular-surface-disease
#18
Ahmad Kheirkhah, Antonio Di Zazzo, Vannarut Satitpitakul, Merle Fernandez, Daniel Magilavy, Reza Dana
PURPOSE: Janus kinase (JAK) and spleen tyrosine kinase (SYK) play critical functions in T-cell activation and in inflammation. Because of their antiinflammatory effects, JAK and SYK inhibitors have recently been evaluated in several immunopathogenic disorders. This pilot study was designed to assess the safety and efficacy of a topical combined JAK/SYK inhibitor, R348, ophthalmic solution for treatment of ocular surface disease in graft-versus-host disease (GVHD). METHODS: This phase 2, double-masked, randomized, pilot trial included 30 patients with ocular surface disease due to GVHD who were randomized to receive topical 0...
July 2017: Cornea
https://www.readbyqxmd.com/read/28429420/the-crystal-structure-of-a-new-o-demethylase-from-sphingobium-sp-strain-syk-6
#19
Ayaka Harada, Naofumi Kamimura, Koh Takeuchi, Hong Yang Yu, Eiji Masai, Toshiya Senda
In the cell, tetrahydrofolate (H4 folate) derivatives with a C1 unit are utilized in various ways, such as for the synthesis of amino acids and nucleic acids. While H4 folate derivatives with the C1 unit are typically produced in the glycine cleavage system, Sphingobium sp. strain SYK-6, which can utilize lignin-derived aromatic compounds as a sole source of carbon and energy, lacks this pathway, probably due to its unique nutrient requirements. In this bacterium, H4 folate-dependent O-demethylases in catabolic pathways for lignin-derived aromatic compounds seem to be involved in the C1 metabolism...
April 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28423512/kinase-analysis-of-penile-squamous-cell-carcinoma-on-multiple-platforms-to-identify-potential-therapeutic-targets
#20
Eddy S Yang, Christopher D Willey, Amitkumar Mehta, Michael R Crowley, David K Crossman, Dongquan Chen, Joshua C Anderson, Gurudatta Naik, Deborah L Della Manna, Tiffiny S Cooper, Guru Sonpavde
Penile squamous cell carcinoma (PSCC) is an orphan malignancy with poorly understood biology and suboptimal systemic therapy. Given that kinases may be drivers and readily actionable, we performed comprehensive multiplatform analysis of kinases in PSCC tumor and normal tissue. Fresh frozen tumors were collected from 11 patients with PSCC. After macrodissection to demarcate tumor from normal tissue, the samples underwent multiplatform analysis of kinases. Next Generation Sequencing (NGS) of 517 kinase genes was performed using Agilent Kinome capture and run on the Illumina MiSeq at PE150bp...
March 28, 2017: Oncotarget
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