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syk AND the cell

Aya Furusho, Hiroki Aoki, Satoko Ohno-Urabe, Michihide Nishihara, Saki Hirakata, Norifumi Nishida, Sohei Ito, Makiko Hayashi, Tsutomu Imaizumi, Shinichi Hiromatsu, Hidetoshi Akashi, Hiroyuki Tanaka, Yoshihiro Fukumoto
BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially life-threatening disease that is common in older individuals. Currently, therapeutic options are limited to surgical interventions. Although it has long been known that AAA tissue is enriched in B cells and immunoglobulins, their involvement in AAA pathogenesis remains controversial. METHODS AND RESULTS: We investigated the role of B cells and immunoglobulins in a murine model of AAA, induced with a periaortic application of CaCl2 , and in human AAA...
March 15, 2018: Journal of the American Heart Association
Dongjiao Wang, Sujun Gao, Jintong Chen, Yinghua Zhao, Yuxue Jiang, Xiao Chu, Xiaohua Wang, Ning Liu, Tianxue Qin, Qing Yi, Ying Yue, Siqing Wang
Interleukin-33 (IL-33) is a potent contributor to antiviral immune responses and antitumor immunity. We recently discovered that IL-33 is overexpressed in dectin-1-activated dendritic cells (DCs). However, mechanisms of dectin-1-induced IL-33 expression in DCs remain elusive. Curdlan, an agonist of dectin-1, was used to mature DCs in this study. We found that dectin-1-induced IL-33 expression in DCs relies on Syk and Raf-1 pathways. By using nuclear factor (NF)-κB inhibitors, we also found that dectin-1-induced IL-33 expression relies on NF-κB signaling...
March 14, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Chen Qu, Dandan Zheng, Sai Li, Yingjun Liu, Anna Lidofsky, Jacinta A Holmes, Jianning Chen, Lu He, Lan Wei, Yadi Liao, Hui Yuan, Qimeng Jin, Zelong Lin, Qiaoting Hu, Yuchuan Jiang, Mengxian Tu, Xijun Chen, Weiming Li, Wenyu Lin, Bryan C Fuchs, Raymond T Chung, Jian Hong
Spleen tyrosine kinase (SYK) plays a critical role in immune cell signaling pathways and has been reported as a novel biomarker for human hepatocellular carcinoma (HCC). We sought to investigate the mechanism by which SYK promotes liver fibrosis and to evaluate SYK as a therapeutic target for liver fibrosis. We evaluated the cellular localization of SYK and the association between SYK expression and liver fibrogenesis in normal, HBV-infected, HCV-infected and non-alcoholic steatohepatitis (NASH) liver tissue (n=36, 127, 22 and 30, respectively)...
March 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Alanson W Girton, Narcis I Popescu, Ravi S Keshari, Tarea Burgett, Florea Lupu, K Mark Coggeshall
We showed that human IgG supported the response by human innate immune cells to peptidoglycan (PGN) from Bacillus anthracis and PGN-induced complement activation. However, other serum constituents have been shown to interact with peptidoglycan, including the IgG-like soluble pattern recognition receptor serum amyloid P (SAP). Here, we compared the ability of SAP and of IgG to support monocyte and complement responses to PGN. Utilizing in vitro methods, we demonstrate that SAP is superior to IgG in supporting monocyte production of cytokines in response PGN...
March 12, 2018: Infection and Immunity
Kenji Takahashi, Kyohei Miyake, Shojiro Hishiyama, Naofumi Kamimura, Eiji Masai
Sphingobium sp. strain SYK-6 is able to use a phenylcoumaran-type biaryl, dehydrodiconiferyl alcohol (DCA), as a sole source of carbon and energy. In SYK-6 cells, the alcohol group of the B-ring side chain of DCA was first oxidized to the carboxyl group, and then the alcohol group of the A-ring side chain was oxidized to generate 5-(2-carboxyvinyl)-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-2,3-dihydrobenzofuran-3-carboxylate (DCA-CC). We identified phcF, phcG, and phcH, which conferred the ability to convert DCA-CC into 3-(4-hydroxy-3-(4-hydroxy-3-methoxystyryl)-5-methoxyphenyl)acrylate (DCA-S) in a host strain...
March 12, 2018: Environmental Microbiology
Seung Geun Yeo, Yong Sung Won, Sang Hoon Kim, Dong Choon Park
Endometriosis, although not malignant, has clinically demonstrated properties of invasiveness and metastasis. The pathogenesis of endometriosis, however, has not yet been elucidated. The immunological differences between endometriosis and malignant gynecologic tumors were analyzed by assessing C-type lectin receptors, which are associated with innate immunity, and immunoglobulin secretion, which is associated with B cell adaptive immunity, in the peritoneal fluid of these patients. Peritoneal fluid samples were obtained from 42 patients with benign masses (control group), 38 with endometriosis, and 43 with gynecologic (ovarian, uterine, and cervical) cancers...
2018: International Journal of Medical Sciences
Dehua Liu, Ben Chung-Lap Chan, Ling Cheng, Miranda Sin-Man Tsang, Jing Zhu, Chun-Wai Wong, Delong Jiao, Helen Yau-Tsz Chan, Ping Chung Leung, Christopher Wai-Kei Lam, Chun Kwok Wong
The immune system responds to Mycobacterium tuberculosis (MTB) infection by forming granulomas to quarantine the bacteria from spreading. Granuloma-mediated inflammation is a cause of lung destruction and disease transmission. Sophora flavescens (SF) has been demonstrated to exhibit bactericidal activities against MTB. However, its immune modulatory activities on MTB-mediated granulomatous inflammation have not been reported. In the present study, we found that flavonoids from Sophora flavescens (FSF) significantly suppressed the pro-inflammatory mediators released from mouse lung alveolar macrophages (MH-S) upon stimulation by trehalose dimycolate (TDM), the most abundant lipoglycan on MTB surface...
March 2, 2018: Scientific Reports
Unni K Samavedam, Nina Mitschker, Anika Kasprick, Katja Bieber, Enno Schmidt, Tamás Laskay, Andreas Recke, S Goletz, Gestur Vidarsson, Franziska S Schulze, Mikko Armbrust, Katharina Schulze Dieckhoff, Hendri H Pas, Marcel F Jonkman, Kathrin Kalies, Detlef Zillikens, Yask Gupta, Saleh M Ibrahim, Ralf J Ludwig
Because of the morbidity and limited therapeutic options of autoimmune diseases, there is a high, and thus far, unmet medical need for development of novel treatments. Pemphigoid diseases, such as epidermolysis bullosa acquisita (EBA), are prototypical autoimmune diseases that are caused by autoantibodies targeting structural proteins of the skin, leading to inflammation, mediated by myeloid cells. To identify novel treatment targets, we performed cutaneous genome-wide mRNA expression profiling in 190 outbred mice after EBA induction...
2018: Frontiers in Immunology
Ivo S Hansen, Lisette Krabbendam, Jochem H Bernink, Fabricio Loayza-Puch, Willianne Hoepel, Johan A van Burgsteden, Elsa C Kuijper, Christianne J Buskens, Willem A Bemelman, Sebastiaan A J Zaat, Reuven Agami, Gestur Vidarsson, Gijs R van den Brink, Esther C de Jong, Manon E Wildenberg, Dominique L P Baeten, Bart Everts, Jeroen den Dunnen
CD103+ dendritic cells (DC) are crucial for regulation of intestinal tolerance in humans. However, upon infection of the lamina propria this tolerogenic response is converted to an inflammatory response. Here we show that immunoglobulin A (IgA) immune complexes (IgA-IC), which are present after bacterial infection of the lamina propria, are important for the induction of inflammation by the human CD103+ SIRPα+ DC subset. IgA-IC, by recognition through FcαRI, selectively amplify the production of proinflammatory cytokines TNF, IL-1β and IL-23 by human CD103+ DCs...
February 28, 2018: Nature Communications
Mubashshir Rasheed, Anamika Battu, Rupinder Kaur
A family of 11 cell surface-associated aspartyl proteases (CgYps1-11), also referred as yapsins, is a key virulence factor in the pathogenic yeast Candida glabrata. However, the mechanism by which CgYapsins modulate immune response and facilitate survival in the mammalian host, remains to be identified. Here, using RNA-Seq analysis, we report that genes involved in cell wall metabolism are differentially regulated in the Cgyps1-11Δ mutant. Consistently, the mutant contained lower β-glucan and mannan levels and exhibited increased chitin content in the cell wall...
February 28, 2018: Journal of Biological Chemistry
Matthew Wagener, J Claire Hoving, Hlumani Ndlovu, Mohlopheni J Marakalala
One of the first steps toward mounting an effective immune response to Mycobacterium tuberculosis (Mtb) is recognition of the pathogen through pattern-recognition receptors (PRRs) expressed by innate immune cells. Activation of the PRR Dectin-1 by an unknown mycobacterial ligand triggers an intracellular signaling cascade involving numerous proteins, including spleen tyrosine kinase, protein kinase C-delta, and caspase recruitment domain family member 9, some of which have been shown to influence host immune response to TB infection...
2018: Frontiers in Immunology
Ha-Kyoung Kwon, Woo-Ri Jo, Hye-Jin Park
BACKGROUND: Cordyceps militaris (C. militaris) is reported to exert various immune-activities. To enhance its activity, we fermented C.militaris with Pediococcus pentosaceus ON89A (GRC-ON89A). In this study, we investigated the immune-enhancing activity GRC-ON89A, using immunosuppressed model. METHODS: Immunosuppression was induced by intraperitoneal injection of cyclophosphamide (CY). Each group was orally administered distilled water, GRC-ON89A or GRC, respectively...
February 23, 2018: BMC Complementary and Alternative Medicine
Pierre H Mangin, Marie-Blanche Onselaer, Nicolas Receveur, Nicolas Le Lay, Alexander T Hardy, Clare Wilson, Ximena Sanchez, Stephane Loyau, Arnaud Dupuis, Amir K Babar, Jeanette Lc Miller, Helen Philippou, Craig E Hughes, Andrew B Herr, Robert As Ariëns, Diego Mezzano, Martine Jandrot-Perrus, Christian Gachet, Steve P Watson
GPVI, a major platelet activation receptor for collagen and fibrin, is considered as a particularly promising safe antithrombotic target. In this study, we show that human GPVI signals upon platelet adhesion to fibrinogen. Full spreading of human platelets on fibrinogen is abolished in platelets from GPVI-deficient patients suggesting that fibrinogen activates platelets through GPVI. While mouse platelets fail to spread on fibrinogen, human-GPVI-transgenic mouse platelets show full spreading and increased Ca2+ signalling through the tyrosine kinase Syk...
February 22, 2018: Haematologica
Riccardo Bomben, Simone Ferrero, Tiziana D'Agaro, Michele Dal Bo, Alessandro Re, Andrea Evangelista, Angelo Michele Carella, Alberto Zamò, Umberto Vitolo, Paola Omedè, Chiara Rusconi, Luca Arcaini, Luigi Rigacci, Stefano Luminari, Andrea Piccin, Delong Liu, Adrien Wiestner, Gianluca Gaidano, Sergio Cortelazzo, Marco Ladetto, Valter Gattei
Mantle cell lymphoma patients have variable clinical courses, ranging from indolent cases not requiring immediate treatment to aggressive, rapidly progressing diseases. Thus, diagnostic tools capable to stratify patients according to their risk of relapse and death are warranted. The study included 83 samples from the Fondazione Italiana Linfomi MCL-0208 clinical trial. Through gene expression profiling and quantitative real-time PCR we analyzed 46 peripheral blood and 43 formalin-fixed paraffin-embedded lymph node samples...
February 22, 2018: Haematologica
Amr Al-Haidari, Anwar Algaber, Raed Madhi, Ingvar Syk, Henrik Thorlacius
Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the worst prognostic factor for patients with CRC. HuR (ELAVL1) is overexpressed in CRC and has been reported to promote colon cancer growth by targeting RNA in the cell cytoplasm. Herein, the role of miR-155-5p in regulating HuR expression and cell migration was examined in colon cancer cells. MiR-155-5p knockdown in serum-starved colon cancer cells decreased both colon cancer cell chemotaxis and cytoplasmic expression of HuR...
February 19, 2018: Cancer Letters
Jun Liu, Hanying Zhu, Jiawen Qian, Ermeng Xiong, Lumin Zhang, Yan-Qing Wang, Yiwei Chu, Hiromi Kubagawa, Takeshi Tsubata, Ji-Yang Wang
The marginal zone B cells (MZB) are located at the interface between the circulation and lymphoid tissue and as a gatekeeper play important roles in both innate and adaptive immune responses. We have previously found that MZB are significantly reduced in mice deficient in the IgM Fc receptor (FcμR) but how FcμR regulates the development and function of MZB remains unknown. In this study, we found that both marginal zone precursor (MZP) and MZB were decreased in FcμR -/- mice. The reduction of MZP and MZB was not due to impaired proliferation of these cells but rather due to their increased death...
2018: Frontiers in Immunology
Wayne S Kontur, Craig A Bingman, Charles N Olmsted, Douglas R Wassarman, Arne Ulbrich, Daniel L Gall, Robert W Smith, Larissa M Yusko, Brian G Fox, Daniel R Noguera, Joshua J Coon, Timothy J Donohue
As a major component of plant cells walls, lignin is a potential renewable source of valuable chemicals. Several sphingomonad bacteria have been identified that can break the β-aryl ether bond connecting most phenylpropanoid units of the lignin heteropolymer. Here, we tested three sphingomonads predicted to be capable of breaking the β-aryl ether bond of the dimeric aromatic compound guaiacylglycerol-β-guaiacyl ether (GGE) and found that Novosphingobium aromaticivorans metabolizes GGE at one of the fastest rates thus far reported...
February 15, 2018: Journal of Biological Chemistry
Lina Antenucci, Vesa P Hytönen, Jari Ylänne
Spleen tyrosine kinase (Syk) is involved in cellular adhesion and also in the activation and development of hematopoietic cells. Syk activation induced by genomic rearrangement has been linked to certain T-cell lymphomas, and Syk inhibitors have been shown to prolong survival of patients with B-cell lineage malignancies. Syk is activated either by its interaction with a double-phosphorylated Immunoreceptor Tyrosine-based Activation Motif (pITAM), which induces rearrangements in the Syk structure, or by the phosphorylation of specific tyrosine residues...
February 12, 2018: Journal of Biological Chemistry
Yugai Jia, Yumeng Miao, Mengfan Yue, Mei Shu, Zhifeng Wei, Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid, was previously demonstrated to attenuate inflammation and cartilage destruction in the ankles of mice with collagen-induced arthritis (CIA). Here, we explored the underlying mechanism by which tetrandrine prevented arthritis-induced bone erosion by focusing on the differentiation and function of osteoclasts. We found that daily administration of tetrandrine (30 mg/kg) markedly reduced the bone damage and decreased the number of osteoclasts in CIA rats. In vitro, tetrandrine inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis at the early stage and reduced the expressions of osteoclast-related marker genes...
January 30, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Gerald Moncayo, Michal Grzmil, Tatiana Smirnova, Pawel Zmarz, Roland M Huber, Debby Hynx, Hubertus Kohler, Yuhua Wang, Hans-Rudolf Hotz, Nancy E Hynes, Georg Keller, Stephan Frank, Adrian Merlo, Brian A Hemmings
Background: Glioblastoma (GBM) is one of the most aggressive human brain tumors with a median survival of 15-18 months. There is a desperate need to find novel therapeutic targets. Various receptor protein kinases have been identified as potential targets; however, response rates in clinical studies have been somewhat disappointing. Targeting the Spleen Tyrosine Kinase (SYK), which acts downstream of a range of oncogenic receptors, may therefore show more promising results. Methods: Kinase expression of brain tumor samples including GBM and low-grade tumors were compared to normal brain and normal human astrocytes (NHA) by microarray analysis...
February 1, 2018: Neuro-oncology
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