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https://www.readbyqxmd.com/read/28723667/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#1
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
June 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#2
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28722110/renal-infiltrating-cd11c-cells-are-pathogenic-in-murine-lupus-nephritis-through-promoting-cd4-t-cell-responses
#3
Xiaofeng Liao, Jingjing Ren, Alec Reihl, Tharshikha Pirapakaran, Bharath Sreekumar, Thomas E Cecere, Christopher M Reilly, Xin M Luo
Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE) causing morbidity and mortality in 40-60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone mice. These cells may play important pathogenic or regulatory roles in situ to promote or sustain LN. Here, using lupus-prone mouse models, we showed the pathogenic role of a kidney-infiltrating CD11c(+) myeloid cell population in LN...
July 19, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28720906/trail-tnf-related-apoptosis-inducing-ligand-induces-an-inflammatory-response-in-human-adipocytes
#4
Verena Zoller, Jan-Bernd Funcke, Julian Roos, Meike Dahlhaus, Muad Abd El Hay, Karlheinz Holzmann, Ralf Marienfeld, Thomas Kietzmann, Klaus-Michael Debatin, Martin Wabitsch, Pamela Fischer-Posovszky
High serum concentrations of TNF-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor protein family, are found in patients with increased BMI and serum lipid levels. In a model of murine obesity, both the expression of TRAIL and its receptor (TRAIL-R) is elevated in adipose tissue. Accordingly, TRAIL has been proposed as an important mediator of adipose tissue inflammation and obesity-associated diseases. The aim of this study was to investigate if TRAIL regulates inflammatory processes at the level of the adipocyte...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718014/protein-hydrolysate-from-canned-sardine-and-brewing-by-products-improves-tnf-%C3%AE-induced-inflammation-in-an-intestinal-endothelial-co-culture-cell-model
#5
Elsa F Vieira, John Van Camp, Isabel M P L V O Ferreira, Charlotte Grootaert
PURPOSE: The anti-inflammatory activity of sardine protein hydrolysates (SPH) obtained by hydrolysis with proteases from brewing yeast surplus was ascertained. METHODS: For this purpose, a digested and desalted SPH fraction with molecular weight lower than 10 kDa was investigated using an endothelial cell line (EA.hy926) as such and in a co-culture model with an intestinal cell line (Caco-2). Effects of SPH <10 kDa on nitric oxide (NO) production, reactive oxygen species (ROS) inhibition and secretion of monocyte chemoattractant protein 1 (MCP-1), vascular endothelial growth factor (VEGF), chemokine IL-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) were evaluated in TNF-α-treated and untreated cells...
July 17, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28717358/clinical-response-to-vedolizumab-in-ulcerative-colitis-patients-is-associated-with-changes-in-integrin-expression-profiles
#6
Friederike Fuchs, Daniela Schillinger, Raja Atreya, Simon Hirschmann, Sarah Fischer, Clemens Neufert, Imke Atreya, Markus F Neurath, Sebastian Zundler
BACKGROUND: Despite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear. METHODS: Blood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28717346/inflammatory-wnt5a-signalling-pathways-affecting-barrier-function-of-human-vascular-endothelial-cells
#7
Tom Skaria, Gabriele Schoedon
Wnt5A is a chemokine secreted by inflammatory-activated human macrophages that sustains their inflammatory response in an autocrine manner. High levels of Wnt5A are found in sera of patients with sepsis and septic shock. Here, we comment on recently reported Wnt5A signalling pathways in human vascular endothelial cells (VEC). In human VEC, Wnt5A regulates cytoskeleton remodelling and barrier function through Ryk receptor and Rho-associated protein serine/threonine kinase, targeting LIMK2 and CFL1 involved in actin polymerisation...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28717168/dynamics-and-function-of-cxcr4-in-formation-of-the-granule-cell-layer-during-hippocampal-development
#8
Yuka Mimura-Yamamoto, Hiroshi Shinohara, Taichi Kashiwagi, Toru Sato, Seiji Shioda, Tatsunori Seki
In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717003/surface-toll-like-receptor-3-expression-in-metastatic-intestinal-epithelial-cells-induces-inflammatory-cytokine-production-and-promotes-invasiveness
#9
Marit Bugge, Bjarte Bergstrom, Oda Kamilla Eide, Helene Solli, Ingrid F Kjønstad, Jørgen Stenvik, Terje Espevik, Nadra J Nilsen
Toll-like receptors (TLR)s are innate immune receptors for sensing microbial molecules and damage-associated molecular patterns released from host cells. Double-stranded RNA and the synthetic analog polyinosinic:polycytidylic acid (Poly(I:C)) bind and activate TLR3. This stimulation leads to recruitment of the adaptor molecule TRIF and activation of the transcription factors nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF-3), classically inducing IFNβ production. Here, we report that unlike non-metastatic intestinal epithelial cells (IECs), metastatic IECs express TLR3, and that TLR3 promotes invasiveness of these cells...
July 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28716963/chemokine-ccl2-ccr2-signaling-induces-neuronal-cell-death-via-stat3-activation-and-il-1%C3%AE-production-after-status-epilepticus
#10
Dai-Shi Tian, Jiyun Peng, Madhuvika Murugan, Lijie Feng, Jun-Li Liu, Ukpong B Eyo, Li-Jun Zhou, Rochelle Mogilevsky, Wei Wang, Long-Jun Wu
Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1(GFP/+):CCR2(RFP/+) double transgenic mice, we demonstrated that CCL2-CCR2 signaling participated in resident microglial activation and blood-derived monocyte infiltration...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28716390/impact-of-cytokine-genetic-polymorphisms-on-the-risk-of-renal-parenchymal-infection-in-children
#11
Almontaser Hussein, Eman Askar, Ahlam Badawy, Khaled Saad, Asmaa Zahran, Ahmad A Elderwy
BACKGROUND: Acute pyelonephritis is associated with renal scarring in up to 30% of patients. Renal scarring may cause significant long-term morbidity. The pathogenesis of acute pyelonephritis remains unclear, although it involves interaction among uroepithelium, the immune system cells, and the locally produced cytokines. That some UTI-prone children develop acute pyelonephritis, and eventually renal parenchymal scarring, suggests a genetic role. Interleukin-6, interleukin-8, chemokine receptor-1 (CXCR1), and tumor necrosis factor-alpha (TNFα), the key regulators of the host immune responses, are proteins whose secretion is controlled by genes...
July 3, 2017: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/28716095/development-of-real-time-and-lateral-flow-dipstick-recombinase-polymerase-amplification-assays-for-rapid-detection-of-goatpox-virus-and-sheeppox-virus
#12
Yang Yang, Xiaodong Qin, Xiangle Zhang, Zhixun Zhao, Wei Zhang, Xueliang Zhu, Guozheng Cong, Yanmin Li, Zhidong Zhang
BACKGROUND: Goatpox virus (GTPV) and sheeppox virus (SPPV), which belong to the Capripoxvirus (CaPV), are economically important pathogens of small ruminants. Therefore, a sensitive, specific and rapid diagnostic assay for detection of GTPV and SPPV is necessary to accurately and promptly control these diseases. METHODS: Recombinase polymerase amplification (RPA) assays combined with a real-time fluorescent detection (real-time RPA assay) and lateral flow dipstick (RPA LFD assay) were developed targeting the CaPV G-protein-coupled chemokine receptor (GPCR) gene, respectively...
July 17, 2017: Virology Journal
https://www.readbyqxmd.com/read/28715645/characteristics-of-regulatory-b-cells-in-patients-with-chronic-hepatitis-b-virus-infection-in-different-immune-phases
#13
Guiyang Wang, Yong Liu, Rui Huang, Bei Jia, Ran Su, Zhenhua Sun, Chen Tian, Yali Xiong, Juan Xia, Xiaomin Yan, Zhaoping Zhang, Chao Wu
Regulatory B cells (Bregs) are reported to play an important role in the immune responses to chronic hepatitis B virus (HBV) via Toll-like-receptors (TLRs) signaling. We aimed to investigate the characteristics of Bregs and the expressions of TLRs in Bregs in the peripheral blood of different immune phases of patients with chronic HBV infection. In this study, we determined the frequencies of Bregs and TLR9, TLR2, and TLR4 in peripheral blood using flow cytometry and determined the levels of IL-10 in serum with the Human Magnetic Cytokine/Chemokine Bead Panel...
May 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28714969/endothelial-notch-signalling-limits-angiogenesis-via-control-of-artery-formation
#14
Sana S Hasan, Roman Tsaryk, Martin Lange, Laura Wisniewski, John C Moore, Nathan D Lawson, Karolina Wojciechowska, Hans Schnittler, Arndt F Siekmann
Angiogenic sprouting needs to be tightly controlled. It has been suggested that the Notch ligand dll4 expressed in leading tip cells restricts angiogenesis by activating Notch signalling in trailing stalk cells. Here, we show using live imaging in zebrafish that activation of Notch signalling is rather required in tip cells. Notch activation initially triggers expression of the chemokine receptor cxcr4a. This allows for proper tip cell migration and connection to the pre-existing arterial circulation, ultimately establishing functional arterial-venous blood flow patterns...
July 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28714968/dll4-and-notch-signalling-couples-sprouting-angiogenesis-and-artery-formation
#15
Mara E Pitulescu, Inga Schmidt, Benedetto Daniele Giaimo, Tobiah Antoine, Frank Berkenfeld, Francesca Ferrante, Hongryeol Park, Manuel Ehling, Daniel Biljes, Susana F Rocha, Urs H Langen, Martin Stehling, Takashi Nagasawa, Napoleone Ferrara, Tilman Borggrefe, Ralf H Adams
Endothelial sprouting and proliferation are tightly coordinated processes mediating the formation of new blood vessels during physiological and pathological angiogenesis. Endothelial tip cells lead sprouts and are thought to suppress tip-like behaviour in adjacent stalk endothelial cells by activating Notch. Here, we show with genetic experiments in postnatal mice that the level of active Notch signalling is more important than the direct Dll4-mediated cell-cell communication between endothelial cells. We identify endothelial expression of VEGF-A and of the chemokine receptor CXCR4 as key processes controlling Notch-dependent vessel growth...
July 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28714865/microglia-in-prion-diseases
#16
Adriano Aguzzi, Caihong Zhu
Prion diseases are a group of progressive and fatal neurodegenerative disorders characterized by deposition of scrapie prion protein (PrPSc) in the CNS. This deposition is accompanied by neuronal loss, spongiform change, astrogliosis, and conspicuous microglial activation. Here, we argue that microglia play an overall neuroprotective role in prion pathogenesis. Several microglia-related molecules, such as Toll-like receptors (TLRs), the complement system, cytokines, chemokines, inflammatory regulators, and phagocytosis mediators, are involved in prion pathogenesis...
July 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28714025/effect-of-ccl2-sirna-on-proliferation-and-apoptosis-in-the-u251-human-glioma-cell-line
#17
Bin Lu, Yue Zhou, Zhongzhou Su, Ai Yan, Peng Ding
Glioma is one of the most common types of tumor of the central nervous system. Increased expression of C‑C motif chemokine 2 (CCL2) has previously been observed in various types of cancer. The effect of CCL2 small interfering (si)RNA on the proliferation, angiogenesis and apoptosis of the glioma cell line U251 was investigated in the present study. Data on CCL2 expression in glioma and normal tissues were obtained from The Cancer Genome Atlas. A total of 30 patients with glioma were enrolled in the present study...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713812/the-biology-of-eosinophils-and-their-role-in-asthma
#18
REVIEW
Claire N McBrien, Andrew Menzies-Gow
This review will describe the structure and function of the eosinophil. The roles of several relevant cell surface molecules and receptors will be discussed. We will also explore the systemic and local processes triggering eosinophil differentiation, maturation, and migration to the lungs in asthma, as well as the cytokine-mediated pathways that result in eosinophil activation and degranulation, i.e., the release of multiple pro-inflammatory substances from eosinophil-specific granules, including cationic proteins, cytokines, chemokines growth factors, and enzymes...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28711757/cxcr4-and-cxcr7-play-distinct-roles-in-cardiac-lineage-specification-and-pharmacologic-%C3%AE-adrenergic-response
#19
Delaine K Ceholski, Irene C Turnbull, Venu Pothula, Laura Lecce, Andrew A Jarrah, Changwon Kho, Ahyoung Lee, Lahouaria Hadri, Kevin D Costa, Roger J Hajjar, Sima T Tarzami
CXCR4 and CXCR7 are prominent G protein-coupled receptors (GPCRs) for chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). This study demonstrates that CXCR4 and CXCR7 induce differential effects during cardiac lineage differentiation and β-adrenergic response in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using lentiviral vectors to ablate CXCR4 and/or CXCR7 expression, hiPSC-CMs were tested for phenotypic and functional properties due to gene knockdown. Gene expression and flow cytometry confirmed the pluripotent and cardiomyocyte phenotype of undifferentiated and differentiated hiPSCs, respectively...
July 8, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28711492/species-specific-real-time-rt-pcr-analysis-of-expression-of-stromal-cell-genes-in-a-tumor-xenotransplantation-model-in-mice
#20
Evzen Krepela, Petr Busek, Marek Hilser, Zdislava Vanickova, Aleksi Sedo
Human tumor xenografts in mice together with the species-specific analysis of expressed genes allow to study the molecular processes driving tumor growth and progression in vivo and help to develop and evaluate anticancer therapies. In the present work, we designed and validated species-specific real-time RT-PCR assays for discrimination and quantitation of expression of human and mouse transcripts in cancer and stromal cells including dipeptidyl peptidase (DPP) 4, DPP8, DPP9, fibroblast activation protein (FAP) and CXC chemokine receptor 4 in mixed human-mouse biological samples...
July 12, 2017: Biochemical and Biophysical Research Communications
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