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https://www.readbyqxmd.com/read/28642278/rheumatoid-arthritis-and-psoriatic-arthritis-synovial-fluid-stimulates-prolactin-production-by-macrophages
#1
Man Wai Tang, Samuel Garcia, Beatriz Malvar Fernandez, Danielle M Gerlag, Paul-Peter Tak, Kris A Reedquist
Prolactin (PRL) is a neuroendocrine hormone that can promote inflammation. We examined the synovial tissue and fluid levels of PRL in patients with inflammatory arthritis, PRL expression in differentiated Mϕs from patients with arthritis and from healthy donors, and the effects of different stimuli on PRL production by Mϕs. PRL levels were measured in paired synovial fluid (SF) and peripheral blood of patients with rheumatoid arthritis (RA, n = 19), psoriatic arthritis (PsA, n = 11), and gout (n = 11). Synovial-tissue PRL mRNA expression was measured by quantitative PCR in patients with RA (n = 25), PsA (n = 11), and gout (n = 12) and in Mϕs differentiated in SF of patients with RA, PsA, other subtypes of spondyloarthritis (SpA), and gout...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28623810/platelet-granule-release-is-associated-with-reactive-oxygen-species-generation-during-platelet-storage-a-direct-link-between-platelet-pro-inflammatory-and-oxidation-states
#2
Mehran Ghasemzadeh, Ehteramolsadat Hosseini
BACKGROUND: Upon platelet stimulation with agonists, reactive oxygen species (ROS) generation enhances platelet activation and granule release. Whether ROS generation during platelet storage could be directly correlated with the expression of proinflammatory molecules and granule release has been investigated in this study. MATERIAL AND METHOD: PRP-platelet concentrates were subjected to flowcytometry analysis to assess the expression of platelet activation marker, P-selectin and CD40L during storage...
June 10, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28623659/immune-activation-of-platelets-in-response-to-serial-phlebotomy-in-pigtailed-macaques-macaca-nemestrina
#3
Kelly A Metcalf Pate, Meghan S Vermillion, Claire E Lyons, Kevin M Najarro, Robert J Adams
Serial phlebotomy is a common sampling practice for repeated-measures studies in biomedical research. In NHP, the effect ofserial blood collection on RBC parameters has been characterized, but the effects on platelet parameters and other aspects of thehemogram have not been well studied. We sought to characterize the circulating platelet phenotype throughout the course of 7serial phlebotomies spanning 30 d in pigtailed macaques (Macaca nemestrina). Phlebotomy was performed on 23 animals at days0, 2, 4, 7, 10, 21, and 30 to quantify the circulating platelet count and markers of both hemostatic and immune platelet activation...
June 16, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28623282/a-nationwide-study-of-severe-and-protracted-diarrhoea-in-patients-with-primary-immunodeficiency-diseases
#4
Wen-I Lee, Chien-Chang Chen, Tang-Her Jaing, Liang-Shiou Ou, Chuen Hsueh, Jing-Long Huang
Diarrhoea lasting longer than 14 days and failing to respond to conventional management is defined as severe and protracted diarrhoea (SD). In this study, we investigated the prevalence, pathogens and prognosis of SD in primary immunodeficiency diseases (PIDs). Among 246 patients with predominantly paediatric-onset PIDs from 2003-2015, 21 [Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each)] and five [CVID (four), SCID (one)] without identified mutations had SD before prophylactic treatment...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28609750/association-of-plasma-cd40l-with-acute-chest-syndrome-in-sickle-cell-anemia
#5
Vanessa Tonin Garrido, Laura Sonzogni, Siana Nkya Mtatiro, Fernando F Costa, Nicola Conran, Swee Lay Thein
Platelet activation and platelet-derived cytokines contribute to the vascular inflammation and increased thrombotic activity known to occur in patients with sickle cell anemia (SCA). CD40 ligand (CD40L), a platelet-associated pro-inflammatory molecule that promotes endothelial cell activation, is elevated in the circulation of SCA patients. We sought to evaluate the association of CD40L and inflammation with sickle-related clinical complications and laboratory variables in SCA patients. Soluble CD40L, thrombospondin (TSP)-1 and tumor necrosis factor (TNF)-α were determined in the platelet-poor plasma of healthy individuals and steady-state SCA patients by ELISA...
June 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28589354/crispr-cas9-mediated-in-vitro-mutagenesis-in-gc-like-b-cells
#6
Van Trung Chu, Robin Graf, Klaus Rajewsky
The CRISPR/Cas9 technology has developed into a powerful tool for genome editing, both in terms of gene silencing and the insertion of precise mutations. However, the application of CRISPR/Cas9-mediated mutagenesis in primary immune cells, in particular in B cells, is still in its infancy because of the difficulty to deliver the CRISPR/Cas9 system into these cells. Here, we describe a new method to use CRISPR/Cas9 for manipulating genes in germinal center (GC)-like B cells in vitro. We isolated Cas9-expressing B cells from R26-Cas9iGFP/+ mice (expressing Cas9 constitutively from the Rosa26 locus) and mixed them with control B cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28583714/il-21-anti-tim1-cd40-ligand-promotes-b10-activity-in-vitro-and-alleviates-bone-loss-in-experimental-periodontitis-in-vivo
#7
Yang Hu, Pei Yu, Xinbo Yu, Xingxue Hu, Toshihisa Kawai, Xiaozhe Han
IL-10-expressing regulatory B cells (B10) play an essential role in immune system balance by suppressing excessive inflammatory responses. In this study, we investigated induction of B 10 cell's IL-10 competency in vitro and its effect on ligature-induced experimental periodontitis in vivo. Spleen B cells were isolated from C57BL/6J mice and cultured for 48 hours under the following conditions: control, CD40L, IL-21, anti-Tim1, CD40L+IL-21, CD40L+anti-Tim1, CD40L+IL-21+anti-Tim1. Silk ligatures were tied around both maxillary second molars of C57BL/6J mice for two weeks...
June 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28567041/pathogen-reactive-t-helper-cell-analysis-in-the-pig
#8
Friederike Ebner, Patrycja Schwiertz, Svenja Steinfelder, Robert Pieper, Jürgen Zentek, Nicole Schütze, Christoph G Baums, Gottfried Alber, Peter Geldhof, Susanne Hartmann
There is growing interest in studying host-pathogen interactions in human-relevant large animal models such as the pig. Despite the progress in developing immunological reagents for porcine T cell research, there is an urgent need to directly assess pathogen-specific T cells-an extremely rare population of cells, but of upmost importance in orchestrating the host immune response to a given pathogen. Here, we established that the activation marker CD154 (CD40L), known from human and mouse studies, identifies also porcine antigen-reactive CD4(+) T lymphocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28559404/peripheral-t-cell-reactivity-to-heat-shock-protein-70-and-its-cofactor-grpe-from-tropheryma-whipplei-is-reduced-in-patients-with-classical-whipple-s-disease
#9
Lucia Trotta, Kathleen Weigt, Katina Schinnerling, Anika Geelhaar-Karsch, Gerrit Oelkers, Federico Biagi, Gino Roberto Corazza, Kristina Allers, Thomas Schneider, Ulrike Erben, Verena Moos
Background: Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response towards Tropheryma (T.) whipplei in genetically predisposed individuals. The cofactor GrpE of heat-shock protein 70 (Hsp70) from T. whipplei was previously identified as B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific pro-inflammatory T-cell responses.Methods: Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before CD40L, CD69, perforin, granzyme B, CD107a, and interferon (IFN)γ were determined in T cells by flow cytometry...
May 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28554543/a-method-for-the-isolation-and-characterization-of-functional-murine-monoclonal-antibodies-by-single-b-cell-cloning
#10
Sara Carbonetti, Brian G Oliver, Vladimir Vigdorovich, Nicholas Dambrauskas, Brandon Sack, Emilee Bergl, Stefan H I Kappe, D Noah Sather
Monoclonal antibody technologies have enabled dramatic advances in immunology, the study of infectious disease, and modern medicine over the past 40years. However, many monoclonal antibody discovery procedures are labor- and time-intensive, low efficiency, and expensive. Here we describe an optimized mAb discovery platform for the rapid and efficient isolation, cloning and characterization of monoclonal antibodies in murine systems. In this platform, antigen-binding splenic B cells from immunized mice are isolated by FACS and cocultured with CD40L positive cells to induce proliferation and mAb production...
May 26, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28551548/quantitative-evaluation-of-atherosclerotic-plaques-and-intraplaque-neovascularization-using-contrast-enhanced-ultrasound-after-treatment-with-atorvastatin-in-rabbits
#11
Hong-Yu Liu, Jia Zhou, Hai Tong, Yan Tang, Xiao-Fang Wang, Qi-Chang Zhou
INTRODUCTION: This study is supposed to investigate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of atherosclerotic plaques and intraplaque neovascularization after treatment with atorvastatin (ATV) in rabbits. MATERIAL AND METHODS: Forty-five New Zealand white rabbits were enrolled to construct the rabbit model of AS. All rabbits were assigned into the control, AS group and ATV groups (n=15 individually). The AS plaque formation and relative parameters were observed and calculated by CEUS respectively...
May 25, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28536390/showing-the-way-oncolytic-adenoviruses-as-chaperones-of-immunostimulatory-adjuncts
#12
REVIEW
Jing Li Huang, Christopher J LaRocca, Masato Yamamoto
Oncolytic adenoviruses (OAds) are increasingly recognized as vectors for immunotherapy in the treatment of various solid tumors. The myriads of advantages of using adenovirus include targeted specificity upon infection and selective replication, which lead to localized viral burst, exponential spread of OAds, and antitumor effect. OAds can also induce a strong immune reaction due to the massive release of tumor antigens upon cytolysis and the presence of viral antigens. This review will highlight recent advances in adenoviral vectors expressing immunostimulatory effectors, such as GM-CSF (granulocyte macrophage colony-stimulating factor), interferon-α, interleukin-12, and CD40L...
September 19, 2016: Biomedicines
https://www.readbyqxmd.com/read/28536305/shaping-the-tumor-stroma-and-sparking-immune-activation-by-cd40-and-4-1bb-signaling-induced-by-an-armed-oncolytic-virus
#13
Emma Eriksson, Ioanna Milenova, Jessica Wenthe, Magnus Ståhle, Justyna Leja-Jarblad, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Angelica Loskog
PURPOSE: Pancreatic cancer is a severe indication with short expected survival despite surgery and/or combination chemotherapeutics. Checkpoint blockade antibodies are approved for several cancer indications but pancreatic cancer has remained refractory. However, there are clinical data suggesting that stimulation of the CD40 pathway may be of interest for these patients. Oncolytic viruses armed with immunostimulatory genes represent an interesting approach. Herein we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activate the CD40 and 4-1BB pathways, respectively...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28527399/the-effects-of-melamine-with-or-without-cyanuric-acid-on-immune-function-in-ovalbumin-sensitized-mice
#14
Rong H Yin, Qiao Dong, Hua S Li, Jing Yuan, Xi T Li, Rong L Yin, Wen Li, Wen C Wang, Bao S Liu, Xiao H Han, Ren F Wang, Xin Wang, Wen L Bai
Melamine is commonly used in the chemical industry, and it has been found to exist on food processing equipment and utensils. Previous investigations suggested that melamine alone or its combination with cyanuric acid appears to be toxic to immune system in animals. The objective of this study is to investigate the potential effects of melamine with or without cyanuric acid on immune function in ovalbumin- sensitized mice. Our data indicated that melamine-related administration caused a significant decreasing in the content of IL-4 in mice in comparison to negative control group...
May 13, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28521278/scaffold-protein-jlp-mediates-tcr-initiated-cd4-t-cell-activation-and-cd154-expression
#15
Qi Yan, Cheng Yang, Qiang Fu, Zhaowei Chen, Shan Liu, Dou Fu, Rahmat N Rahman, Ryota Nakazato, Katsuji Yoshioka, Sam K P Kung, Guohua Ding, Huiming Wang
CD4(+) T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions. Its role in regulating CD4(+) T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4(+) T cells...
May 15, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28518224/t-helper-1-related-molecules-as-well-as-il-15-are-hyperexpressed-in-the-skin-lesions-of-patients-with-pyoderma-gangrenosum
#16
Emiliano Antiga, Roberto Maglie, Walter Volpi, Beatrice Bianchi, Emilio Berti, Angelo Valerio Marzano, Marzia Caproni
Pyoderma gangrenosum (PG) is a rare, immune-mediated skin disease classified into the group of neutrophilic dermatoses. Whether a number of studies confirmed the central role of innate immunity, only few studies investigated the possible contributing role of acquired immunity. In particular, no reports about Th1 and Th2 cells are available yet. Therefore, 15 patients with PG, 5 with Sweet's syndrome (SS) and 9 skin specimens from healthy controls (HC) were investigated, evaluating the expression of Th1-related markers IL-12, IFN-γ, CXCR3, CCR5, of the Th2 related molecules IL-4, IL-5, IL-13 and CCR3, of the co-stimulatory axis CD40/CD40L, of IL-15 and the NK cell marker CD56 in skin lesions by immunohistochemistry...
May 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28512628/dysplasia-of-granulocytes-in-a-patient-with-hpv-disease-recurrent-infections-and-b-lymphopenia-a-novel-variant-of-whim-syndrome
#17
Giusella M F Moscato, Erica Giacobbi, Lucia Anemona, Silvia Di Cesare, Gigliola Di Matteo, Massimo Andreoni, Alessandro Mauriello, Viviana Moschese
WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis. Myelokathexis refers to the retention of mature neutrophils in the bone marrow (BM), which accounts for degenerative changes and hypersegmentation. Most patients present heterozygous autosomal dominant mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 signaling impairs the receptor downregulation causing hyperactivation (gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and the release of neutrophils in the bloodstream...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28494768/inhibition-of-cd40-traf6-interactions-by-the-small-molecule-inhibitor-6877002-reduces-neuroinflammation
#18
Suzanne A B M Aarts, Tom T P Seijkens, Pascal J H Kusters, Susanne M A van der Pol, Barbara Zarzycka, Priscilla D A M Heijnen, Linda Beckers, Myrthe den Toom, Marion J J Gijbels, Louis Boon, Christian Weber, Helga E de Vries, Gerry A F Nicolaes, Christine D Dijkstra, Gijs Kooij, Esther Lutgens
BACKGROUND: The influx of leukocytes into the central nervous system (CNS) is a key hallmark of the chronic neuro-inflammatory disease multiple sclerosis (MS). Strategies that aim to inhibit leukocyte migration across the blood-brain barrier (BBB) are therefore regarded as promising therapeutic approaches to combat MS. As the CD40L-CD40 dyad signals via TNF receptor-associated factor 6 (TRAF6) in myeloid cells to induce inflammation and leukocyte trafficking, we explored the hypothesis that specific inhibition of CD40-TRAF6 interactions can ameliorate neuro-inflammation...
May 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28490810/establishment-of-induced-pluripotent-stem-cells-from-normal-b-cells-and-inducing-aid-expression-in-their-differentiation-into-hematopoietic-progenitor-cells
#19
Fumihiko Kawamura, Makoto Inaki, Atsushi Katafuchi, Yu Abe, Naohiro Tsuyama, Yumiko Kurosu, Aki Yanagi, Mitsunori Higuchi, Satoshi Muto, Takumi Yamaura, Hiroyuki Suzuki, Hideyoshi Noji, Shinichi Suzuki, Mitsuaki A Yoshida, Megumi Sasatani, Kenji Kamiya, Masafumi Onodera, Akira Sakai
B cell derived induced pluripotent stem cells (BiPSCs) were recently established from peripheral blood B cells by the simultaneous transfection of Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) and C/EBPα using a Sendai virus vector. Here, using a different method, we established BiPSCs with immunoglobulin heavy chain (IgH) gene rearrangement from normal B cells purified from lymph nodes. The critical points of our method are pre-stimulation of B cells with IL-21 and CD40-ligand (CD40L), followed by consecutive transfection of highly concentrated Yamanaka factors using a retroviral vector...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489883/bmp-7-induces-apoptosis-in-human-germinal-center-b-cells-and-is-influenced-by-tgf-%C3%AE-receptor-type-i-alk5
#20
Lise K Bollum, Kanutte Huse, Morten P Oksvold, Baoyan Bai, Vera I Hilden, Lise Forfang, Sun Ok Yoon, Sébastien Wälchli, Erlend B Smeland, June H Myklebust
Selection and maturation of B cells into plasma cells producing high-affinity antibodies occur in germinal centers (GC). GCs form transiently in secondary lymphoid organs upon antigen challenge, and the GC reaction is a highly regulated process. TGF-β is a potent negative regulator, but the influence of other family members including bone morphogenetic proteins (BMPs) is less known. Studies of human peripheral blood B lymphocytes showed that BMP-6 suppressed plasmablast differentiation, whereas BMP-7 induced apoptosis...
2017: PloS One
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