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https://www.readbyqxmd.com/read/29138425/timescale-separation-of-positive-and-negative-signaling-creates-history-dependent-responses-to-ige-receptor-stimulation
#1
Brooke Harmon, Lily A Chylek, Yanli Liu, Eshan D Mitra, Avanika Mahajan, Edwin A Saada, Benjamin R Schudel, David A Holowka, Barbara A Baird, Bridget S Wilson, William S Hlavacek, Anup K Singh
The high-affinity receptor for IgE expressed on the surface of mast cells and basophils interacts with antigens, via bound IgE antibody, and triggers secretion of inflammatory mediators that contribute to allergic reactions. To understand how past inputs (memory) influence future inflammatory responses in mast cells, a microfluidic device was used to precisely control exposure of cells to alternating stimulatory and non-stimulatory inputs. We determined that the response to subsequent stimulation depends on the interval of signaling quiescence...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137913/neutrophil-cd16b-crosslinking-induces-lipid-raft-mediated-activation-of-shp-2-and-affects-cytokine-expression-and-retarded-neutrophil-apoptosis
#2
H Yang, H Jiang, Y Song, D J Chen, X J Shen, J H Chen
Two different types of FcRs for IgG are constitutively expressed on the surface of human neutrophils, namely, FcγRIIA (CD32a) and FcγRIIIB (CD16b). Unlike FcγRIIA, FcγRIIIb is GPI anchored to the cell membrane and its signal transduction is still ambiguous. To further understand the signal transduction of CD16b, we compared neutrophil cytokine expression and apoptosis by the cross-linking of CD32a and CD16b respectively. We found that both CD32a and CD16b crosslinking can activate neutrophils, but did not exactly share cytokine expression profiles...
November 11, 2017: Experimental Cell Research
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
#3
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
#4
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/29125235/comparison-of-the-mrna-expression-profile-of-b-cell-receptor-components-in-normal-cd5-high-b-lymphocytes-and-chronic-lymphocytic-leukemia-a-key-role-of-zap70
#5
Aleena A Gladkikh, Daria M Potashnikova, Victor Tatarskiy, Margarita Yastrebova, Alvina Khamidullina, Natasha Barteneva, Ivan Vorobjev
The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils...
November 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29122993/the-microenvironmental-stromal-cells-abrogate-nf-%C3%AE%C2%BAb-inhibitor-induced-apoptosis-in-chronic-lymphocytic-leukemia
#6
Carl Philipp Simon-Gabriel, Katharina Foerster, Shifa Saleem, Dorothee Bleckmann, Marco Benkisser-Petersen, Nicolas Thornton, Kazuo Umezawa, Sarah Decker, Meike Burger, Hendrik Veelken, Rainer Claus, Christine Dierks, Justus Duyster, Katja Zirlik
NF-κB is known to play an important role in the pathogenesis of chronic lymphocytic leukemia. Several NF-κB inhibitors have been shown to successfully induce apoptosis of chronic lymphocytic leukemia cells in vitro. Since the microenvironment is known to be crucial for the survival of chronic lymphocytic leukemia cells, we tested here whether NF-κB inhibition may still induce apoptosis in these leukemic cells in the presence of protective stromal interaction. We used the specific NF-κB inhibitor Dehydroxymethylepoxyquinomicin...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29122990/expression-of-cobll1-encoding-novel-ror1-binding-partner-is-robust-predictor-of-survival-in-chronic-lymphocytic-leukemia
#7
Hana Plešingerová, Pavlína Janovská, Archana Mishra, Lucie Smyčková, Lucie Poppová, Antonín Libra, Karla Plevová, Petra Ovesná, Lenka Radová, Michael Doubek, Šárka Pavlová, Šárka Pospíšilová, Vítězslav Bryja
Chronic lymphocytic leukemia is a disease with upregulated expression of the transmembrane tyrosine-protein kinase ROR1, a member of the Wnt/planar cell polarity pathway. In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic lymphocytic leukemia patients with unmutated IGHV. In the remaining 70% of chronic lymphocytic leukemia patients with unmutated IGHV, COBLL1 expression is low...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29118762/lc3-associated-phagocytosis-is-required-for-dendritic-cell-inflammatory-cytokine-response-to-gut-commensal-yeast-saccharomyces-cerevisiae
#8
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/29118246/serum-iga-immune-complexes-promote-proinflammatory-cytokine-production-by-human-macrophages-monocytes-and-kupffer-cells-through-fc%C3%AE-ri-tlr-cross-talk
#9
Ivo S Hansen, Willianne Hoepel, Sebastiaan A J Zaat, Dominique L P Baeten, Jeroen den Dunnen
IgA is predominantly recognized to play an important role in host defense at mucosal sites, where it prevents invasion of pathogens by neutralization. Although it has recently become clear that IgA also mediates other immunological processes, little remains known about the potential of IgA to actively contribute to induction of inflammation, particularly in nonmucosal organs and tissues. In this article, we provide evidence that immune complex formation of serum IgA plays an important role in orchestration of inflammation in response to pathogens at various nonmucosal sites by eliciting proinflammatory cytokines by human macrophages, monocytes, and Kupffer cells...
November 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29108825/targeting-interferons-and-their-pathways-in-systemic-lupus-erythematosus
#10
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
#11
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/29094492/mechanisms-of-the-action-of-adenine-on-anti-allergic-effects-in-mast-cells
#12
Toru Hosoi, Shinsuke Ino, Fumie Ohnishi, Kenichi Todoroki, Michiko Yoshii, Mai Kakimoto, Christa E Müller, Koichiro Ozawa
INTRODUCTION: Mast cells play an important role in allergic responses. METHODS: We herein demonstrated the mechanisms of inhibitory effect of adenine on IgE/antigen-induced degranulation and TNF-α release in mast cells. RESULTS: We found that these effects were dependent on the amino group of adenine because purine only weakly inhibited degranulation. Adenine also inhibited Ca(2+) ionophore- and thapsigargin-induced degranulation, however, this inhibitory effect was weaker than that of the antigen...
November 1, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29065139/clec9a-modulates-macrophage-mediated-neutrophil-recruitment-in-response-to-heat-killed-mycobacterium-tuberculosis-h37ra
#13
An-Chieh Cheng, Kuang-Yao Yang, Nien-Jung Chen, Tsui-Ling Hsu, Ruwen Jou, Shie-Liang Hsieh, Ping-Hui Tseng
Tuberculosis is a fatal human infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis) that is prevalent worldwide. Mycobacteria differ from other bacteria in that they have a cell wall composed of specific surface glycans that are the major determinant of these organisms' pathogenicity. The interaction of M. tuberculosis with pattern recognition receptors (PRRs), in particular C-type lectin receptors (CLRs), on the surface of macrophages plays a central role in initiating innate and adaptive immunity, but the picture as a whole remains a puzzle...
2017: PloS One
https://www.readbyqxmd.com/read/29055830/pharmacological-inhibition-of-tankyrase-induces-bone-loss-in-mice-by-increasing-osteoclastogenesis
#14
Shunichi Fujita, Tomoyuki Mukai, Takafumi Mito, Shoko Kodama, Akiko Nagasu, Mizuho Kittaka, Teruki Sone, Yasuyoshi Ueki, Yoshitaka Morita
Tankyrase is a poly (ADP-ribose) polymerase that leads to ubiquitination and degradation of target proteins. Since tankyrase inhibitors suppress the degradation of AXIN protein, a negative regulator of the canonical Wnt pathway, they effectively act as Wnt inhibitors. Small molecule tankyrase inhibitors are being investigated as drug candidates for cancer and fibrotic diseases, in which the Wnt pathways are aberrantly activated. Tankyrase is also reported to degrade the adaptor protein SH3BP2 (SH3 domain-binding protein 2)...
October 18, 2017: Bone
https://www.readbyqxmd.com/read/29052597/syk-expression-in-monomorphic-epitheliotropic-intestinal-t-cell-lymphoma
#15
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/29047397/tyrosine-kinase-4-is-involved-in-the-reproduction-of-the-platyhelminth-parasite-schistosoma-japonicum
#16
Han Ding, Fengchun Liu, Lulu Zhu, Fei Wu, Quan Liu, Siyu He, Wei Shao, Yinan Du, Cuiping Ren, Jijia Shen, Miao Liu
BACKGROUND: Schistosomiasis is one of the most common parasitic diseases affecting millions of humans and animals worldwide. Understanding the signal transduction pathways and the molecular basis of reproductive regulation in schistosomes is critically important for developing new strategies for preventing and treating these infections. Syk kinases regulate the proliferation, differentiation, morphogenesis, and survival of various types of cells and have been identified in invertebrates...
October 18, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29031599/interaction-of-dj-1-with-lyn-is-essential-for-ige-mediated-stimulation-of-human-mast-cells
#17
Do-Kyun Kim, Michael A Beaven, Dean D Metcalfe, Ana Olivera
BACKGROUND: DJ-1 is a redox-sensitive protein with multiple roles in cell homeostasis whose levels are altered in mast cell (MC)-related disorders. However, whether DJ-1 can regulate human MC function is unknown. OBJECTIVE: We sought to investigate the potential role of DJ-1 in the responses of human MCs to antigen stimulation. METHODS: DJ-1 was silenced in human CD34(+)-derived and LAD2 MCs using lentiviral sh-RNA constructs. Release of β-hexosaminidase, PGD2 and GM-CSF and changes in reactive oxygen species (ROS) levels were measured after FcεRI engagement...
October 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29020462/syk-inhibitor-r406-down-regulates-inflammation-in-an-in-vitro-model-of-pseudomonas-aeruginosa-infection
#18
Alaa Alhazmi, Joshua Choi, Marina Ulanova
As Pseudomonas aeruginosa infections are characterized by strong inflammation of infected tissues anti-inflammatory therapies in combination with antibiotics have been considered for the treatment of associated diseases. Syk tyrosine kinase is an important regulator of inflammatory responses, and its specific inhibition was explored as a therapeutic option in several inflammatory conditions; however, this has not been studied in bacterial infections. We used a model of in vitro infection of human monocytic cell line THP-1 and lung epithelial cell line H292 with both wild type and flagella-deficient mutant of P...
October 11, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28983472/aspartic-proteases-and-major-cell-wall-components-in-candida-albicans-trigger-the-release-of-neutrophil-extracellular-traps
#19
Marcin Zawrotniak, Oliwia Bochenska, Justyna Karkowska-Kuleta, Karolina Seweryn-Ozog, Wataru Aoki, Mitsuyoshi Ueda, Andrzej Kozik, Maria Rapala-Kozik
Neutrophils use different mechanisms to cope with pathogens that invade the host organism. The most intriguing of these responses is a release of neutrophil extracellular traps (NETs) composed of decondensed chromatin and granular proteins with antimicrobial activity. An important potential target of NETs is Candida albicans-an opportunistic fungal pathogen that employs morphological and phenotype switches and biofilm formation during contact with neutrophils, accompanied by changes in epitope exposition that mask the pathogen from host recognition...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28966111/cationic-liposomes-suppress-intracellular-calcium-ion-concentration-increase-via-inhibition-of-pi3-kinase-pathway-in-mast-cells
#20
Yoshikazu Inoh, Aki Haneda, Satoshi Tadokoro, Satoru Yokawa, Tadahide Furuno
Cationic liposomes are commonly used as vectors to effectively introduce foreign genes (antisense DNA, plasmid DNA, siRNA, etc.) into target cells. Cationic liposomes are also known to affect cellular immunocompetences such as the mast cell function in allergic reactions. In particular, we previously showed that the cationic liposomes bound to the mast cell surface suppress the degranulation induced by cross-linking of high affinity IgE receptors in a time- and dose-dependent manner. This suppression is mediated by impairment of the sustained level of intracellular Ca(2+) concentration ([Ca(2+)]i) via inhibition of store-operated Ca(2+) entry (SOCE)...
December 2017: Biochimica et Biophysica Acta
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