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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
#1
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
#2
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/28886250/dectin-2-is-a-c-type-lectin-receptor-that-recognizes-pneumocystis-and-participates-in-innate-immune-responses
#3
Theodore J Kottom, Deanne M Hebrink, Paige E Jenson, Paige L Marsolek, Marcel Wüthrich, Huafeng Wang, Bruce Klein, Sho Yamasaki, Andrew H Limper
Pneumocystis remains an important fungal pathogen causing life-threatening pneumonia in patients with AIDS and malignancy. Lung fungal pathogens are recognized by C-type Lectin Receptors (CLRs), which bind specific ligands and stimulate innate immune responses. Previously, a role for the CLR Dectin-1 has been shown to mediate immune responses to Pneumocystis spp. For this reason, we investigated a potential role for Dectin-2. Rats with Pneumocystis pneumonia (PCP) exhibited elevated Dectin-2 mRNA levels. Soluble Dectin-2 CRD fusions protein showed binding to intact Pneumocystis carinii (Pc) and to native Pneumocystis major surface glycoprotein/glycoprotein A (Msg/gpA)...
September 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28883531/engineered-proteins-with-sensing-and-activating-modules-for-automated-reprogramming-of-cellular-functions
#4
Jie Sun, Lei Lei, Chih-Ming Tsai, Yi Wang, Yiwen Shi, Mingxing Ouyang, Shaoying Lu, Jihye Seong, Tae-Jin Kim, Pengzhi Wang, Min Huang, Xiangdong Xu, Victor Nizet, Shu Chien, Yingxiao Wang
Protein-based biosensors or activators have been engineered to visualize molecular signals or manipulate cellular functions. Here we integrate these two functionalities into one protein molecule, an integrated sensing and activating protein (iSNAP). A prototype that can detect tyrosine phosphorylation and immediately activate auto-inhibited Shp2 phosphatase, Shp2-iSNAP, is designed through modular assembly. When Shp2-iSNAP is fused to the SIRPα receptor which typically transduces anti-phagocytic signals from the 'don't eat me' CD47 ligand through negative Shp1 signaling, the engineered macrophages not only allow visualization of SIRPα phosphorylation upon CD47 engagement but also rewire the CD47-SIRPα axis into the positive Shp2 signaling, which enhances phagocytosis of opsonized tumor cells...
September 7, 2017: Nature Communications
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
#5
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/28877763/alzheimer-s-disease-pathological-lesions-activate-the-spleen-tyrosine-kinase
#6
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
#7
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...
September 1, 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
#8
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
https://www.readbyqxmd.com/read/28855423/plant-based-food-cyanidin-3-glucoside-modulates-human-platelet-glycoprotein-vi-signaling-and-inhibits-platelet-activation-and-thrombus-formation
#9
Yanling Yao, Yanqiu Chen, Reheman Adili, Thomas McKeown, Pingguo Chen, Guangheng Zhu, Dan Li, Wenhua Ling, Heyu Ni, Yan Yang
Background: Platelets play an important role in hemostasis, thrombosis, and atherosclerosis. Glycoprotein VI (GPVI) is a major platelet receptor that interacts with exposed collagen on injured vessel walls. Our previous studies have shown that anthocyanins (a type of natural plant pigment) attenuate platelet function; however, whether anthocyanins affect collagen-induced GPVI signaling remains unknown.Objective: The objective of this study was to explore the effects of cyanidin-3-glucoside (Cy-3-g, one of the major bioactive compounds in anthocyanins) on platelet activation and thrombosis and the GPVI signaling pathway...
August 30, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28855374/differential-mast-cell-outcomes-are-sensitive-to-fc%C3%AE%C2%B5ri-syk-binding-kinetics
#10
Samantha L Schwartz, Cédric Cleyrat, Mark J Olah, Peter K Relich, Genevieve K Phillips, William S Hlavacek, Keith A Lidke, Bridget S Wilson, Diane S Lidke
Crosslinking of IgE-bound FcεRI triggers multiple cellular responses, including degranulation and cytokine production. Signaling is dependent on recruitment of Syk via docking of its dual SH2 domains to phosphorylated tyrosines within the FcεRI immunoreceptor tyrosine-based activation motifs. Using single molecule imaging in live cells, we directly visualized and quantified the binding of individual mNeonGreen-tagged Syk molecules as they associated with the plasma membrane after FcεRI activation. We found that Syk colocalizes transiently to FcεRI and that Syk-FcεRI binding dynamics are independent of receptor aggregate size...
August 30, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28853956/new-and-emerging-targeted-systemic-therapies-a-new-era-for-atopic-dermatitis
#11
Dylan E Lee, Ashley K Clark, Khiem A Tran, Vivian Y Shi
PURPOSE: This is a review of emerging targeted, systemic therapies for atopic dermatitis (AD). The information presented aims to provide dermatologists with updated therapeutic options, stimulate academic interest, and spark future research. MATERIALS AND METHODS: Extensive search of ClinicalTrials.gov, the National Eczema Association, and PubMed was performed for clinical trials examining the effect of emerging targeted, systemic therapies in patients with AD. Results were included if they demonstrated efficacy in reversing AD symptoms...
August 30, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28840181/measles-virus-nucleocapsid-protein-modulates-the-signal-regulatory-protein-%C3%AE-1-sirp%C3%AE-1-to-enhance-osteoclast-differentiation-in-paget-s-disease-of-bone
#12
Kumaran Sundaram, Yuvaraj Sambandam, Srinivasan Shanmugarajan, D Sudhaker Rao, Sakamuri V Reddy
Paget's disease of bone (PDB) is a chronic localized bone disorder in an elderly population. Environmental factors such as paramyxovirus are implicated in PDB and measles virus nucleocapsid protein (MVNP) has been shown to induce pagetic osteoclasts (OCLs). However, the molecular mechanisms underlying MVNP stimulation of OCL differentiation in the PDB are unclear. We therefore determined the MVNP regulated gene expression profiling during OCL differentiation. Agilent microarray analysis of gene expression identified high levels of SIRPβ1 (353-fold) expression in MVNP transduced human bone marrow mononuclear cells stimulated with RANKL...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/28838991/syk-inhibition-thwarts-the-baff-b-cell-receptor-crosstalk-and-thereby-antagonizes-mcl-1-in-chronic-lymphocytic-leukemia
#13
Cody Paiva, Taylor A Rowland, Bhargava Sreekantham, Claire Godbersen, Scott R Best, Prabhjot Kaur, Marc M Loriaux, Stephen E F Spurgeon, Olga V Danilova, Alexey V Danilov
Although small molecule inhibitors of B-cell receptor-associated kinases revolutionized therapy in chronic lymphocytic leukemia, they provide for incomplete responses. Pro-survival signaling emanating from the microenvironment may foster therapeutic resistance of the malignant B-cells resident in the protective lymphoid niches. BAFF is critical in survival of both healthy and neoplastic B-cells. However, the pro-survival pathways triggered by BAFF have not been fully characterized. Here we show that BAFF elicited resistance to spontaneous and drug-induced apoptosis in stromal co-cultures, induced activation of both canonical and non-canonical NFκB signaling pathways and triggered B-cell receptor signaling in chronic lymphocytic leukemia cells, independent of IGHV mutational status...
August 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28830213/syk-mediated-suppression-of-inflammatory-responses-by-cordyceps-bassiana
#14
Woo Seok Yang, Gyeong Sug Nam, Mi-Yeon Kim, Jae Youl Cho
The fruit body of artificially cultivated Cordyceps bassiana has been reported to exhibit anti-inflammatory and anticancer activities. Although it has been suggested that the fruit body has neutraceutic and pharmaceutic biomaterial potential, the exact anti-inflammatory molecular mechanism has not been fully elucidated. In this study, we demonstrated the immunopharmacologic activity of Cordyceps bassiana under in vitro conditions and investigated its anti-inflammatory mechanism. Water extract (Cm-WE) of the fruit body of artificially cultivated Cordyceps bassiana without polysaccharide fractions reduced the expression of the proinflammatory genes cyclooxygenase (COX)-2, interleukin (IL)-12, and inducible nitric oxide synthase (iNOS) and promoted the expression of the anti-inflammatory gene IL-10 in lipopolysaccharide (LPS)-treated RAW264...
August 22, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28827787/degradation-of-cofilin-is-regulated-by-cbl-aip4-and-syk-resulting-in-increased-migration-of-lmp2a-positive-nasopharyngeal-carcinoma-cells
#15
Murat R Gainullin, Ilya Yu Zhukov, Xiaoying Zhou, Yingxi Mo, Lidiia Astakhova, Ingemar Ernberg, Liudmila Matskova
Expression of cofilin is directly associated with metastatic activity in many tumors. Here, we studied the role of Latent Membrane Protein 2 A (LMP2A) of Epstein-Barr Virus (EBV) in the accumulation of cofilin observed in nasopharyngeal cancer (NPC) tumor cells. We used LMP2A transformed NPC cell lines to analyze cofilin expression. We used mutation analysis, ectopic expression and down-regulation of Cbl, AIP4 and Syk in these cell lines to determine the effect of the LMP2A viral protein on cofilin degradation and its role in the assembly of a cofilin degrading protein complex...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827521/dysivillosins-a-d-unusual-anti-allergic-meroterpenoids-from-the-marine-sponge-dysidea-villosa
#16
Wei-Hua Jiao, Bao-Hui Cheng, Guo-Hua Shi, Guo-Dong Chen, Bin-Bin Gu, Yong-Jun Zhou, Li-Li Hong, Fan Yang, Zhi-Qiang Liu, Shu-Qi Qiu, Zhi-Gang Liu, Ping-Chang Yang, Hou-Wen Lin
Four unusual meroterpenoids, dysivillosins A-D (1-4), were isolated from an organic extract of the marine sponge Dysidea villosa collected from the South China Sea. Their planar structures were determined by 1D and 2D NMR and HRESIMS techniques, while the relative and absolute configurations were elucidated by NOESY experiments and comparison between the calculated and experimental ECD spectra. To the best of our knowledge, dysivillosins A-D are the first examples of terpene-polyketide-pyridine hybrid metabolites from the nature...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819788/insulin-like-growth-factor-1-activates-different-catalytic-subunits-p110-of-pi3k-in-a-cell-type-dependent-manner-to-induce-lipogenesis-dependent-epithelial-mesenchymal-transition-through-the-regulation-of-adam10-and-adam17
#17
Ga Bin Park, Daejin Kim
The activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is critical for the induction of epithelial-mesenchymal transition (EMT) by growth factors, including insulin-like growth factor 1 (IGF-1). The activation of intracellular lipogenesis provides proliferative and survival signals for cancer cells. In this study, we investigated the connection between lipogenesis-related EMT processes and IGF-1-mediated PI3K p110 isoform activation in primary (SW480 cells) and metastatic (SW620) colon carcinoma cells...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28819423/reelin-promotes-adhesion-of-multiple-myeloma-cells-to-bone-marrow-stromal-cells-via-integrin-%C3%AE-1-signaling
#18
Liang Lin, Xinwei Zhang, Li Cao, Quanming An, Jie Hao, Yan Zhang, Rong Jin, Yingjun Chang, Xiaojun Huang, Jin Lu, Qing Ge
The close interaction between tumor cells and bone marrow stromal cells plays a crucial role in the tumorigenesis of multiple myeloma (MM). Reelin, an extracellular matrix protein, is found expressed in myeloma cells and is negatively associated with prognosis. We examined the role of Reelin in myeloma cell adhesion to bone marrow stromal cells and the signaling pathways involved. The results revealed that Reelin promoted the adhesion of myeloma cells to HS-5, a bone marrow stromal cell line, via the activation of β1 integrin...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28813645/lat-is-essential-for-the-mast-cell-stabilising-effect-of-thga-in-ige-mediated-mast-cell-activation
#19
Ji Wei Tan, Daud Ahmad Israf, Nur Fariesha Md Hashim, Yoke Kqueen Cheah, Hanis Hazeera Harith, Khozirah Shaari, Chau Ling Tham
Mast cells play a central role in the pathogenesis of allergic reaction. Activation of mast cells by antigens is strictly dependent on the influx of extracellular calcium that involves a complex interaction between signalling molecules located within the cells. We have previously reported that tHGA, an active compound originally isolated from a local shrub known as Melicope ptelefolia, prevented IgE-mediated mast cell activation and passive systemic anaphylaxis by suppressing the release of interleukin-4 (IL-4) and tumour necrosis factor (TNF)-α from activated rat basophilic leukaemia (RBL)-2H3 cells...
August 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28811826/anti-inflammatory-effect-of-piper-attenuatum-methanol-extract-in-lps-stimulated-inflammatory-responses
#20
You Jin Kim, Jeong Deok, Sunggyu Kim, Deok Hyo Yoon, Gi-Ho Sung, Adithan Aravinthan, Seungihm Lee, Mi-Nam Lee, Suntaek Hong, Jong-Hoon Kim, Young-Jin Son, Jae Youl Cho
Piper attenuatum is used as a traditional medicinal plant in India. One of the substances in P. attenuatum has been suggested to have anti-inflammatory effects. However, there is insufficient research about the anti-inflammatory mechanisms of action of P. attenuatum. The effects of P. attenuatum methanol extract (Pa-ME) on the production of inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2), the expression of proinflammatory genes, the translocation level of transcription factors, and intracellular signaling activities were investigated using macrophages...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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