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https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#1
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28430795/igm-antibodies-to-oxidized-phosphatidylserine-as-protection-markers-in-cardiovascular-disease-among-60-year-olds
#2
Johan Frostegård, Jun Su, Sudhir Sing, Xiang Hua, Max Vikström, Karin Leander, Bruna Gigante, Ulf de Faire, Anna G Frostegård
OBJECTIVE: Phosphatidylserine is exposed on apoptotic cells and is prone to oxidation (OxPS). Here we analyze the association of IgM antibodies against OxPS (anti-OxPS) with the risk of cardiovascular disease (CVD). METHODS: Among sixty-year olds from Stockholm County in Sweden, previously screened for cardiovascular risk factors (2039 men, 2193 women), there were 210 incident CVD-cases identified during a 5-year follow-up. Using a nested case-control design, 622 age- and sex-matched controls were selected...
2017: PloS One
https://www.readbyqxmd.com/read/28428802/regulation-of-th2-responses-by-different-cell-types-expressing-the-interleukin-31-receptor
#3
Saburo Saito, Ayana Aoki, Iwao Arai, Shinya Takaishi, Haruyasu Ito, Nobutake Akiyama, Hiroshi Kiyonari
BACKGROUND: Interleukin-31 (IL-31) is a recently identified cytokine produced by Th2 cells that is involved in the development of atopic dermatitis-induced skin inflammation and pruritus. Its receptor, IL-31RA, is expressed by a number of cell types, including epithelial cells, eosinophils, and activated monocytes and macrophages. To date, however, the regulation of Th2 responses by distinct cell types and tissues expressing IL-31RA has not been well studied. METHODS: In this study, Cry j 2, one of the major allergens of Japanese cedar pollen, was administered to IL-31RA-deficient or wild-type (WT) mice via nasal or intraperitoneal injection for induction of specific Th2 responses...
2017: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/28427157/the-anti-tumor-efficacy-of-3c23k-a-glyco-engineered-humanized-anti-misrii-antibody-in-an-ovarian-cancer-model-is-mainly-mediated-by-engagement-of-immune-effector-cells
#4
Pauline Estupina, Alexandre Fontayne, Jean-Marc Barret, Nathalie Kersual, Olivier Dubreuil, Marion Le Blay, Alexandre Pichard, Marta Jarlier, Martine Pugnière, Maëva Chauvin, Thierry Chardès, Jean-Pierre Pouget, Emmanuel Deshayes, Alexis Rossignol, Toufik Abache, Christophe de Romeuf, Aurélie Terrier, Lucie Verhaeghe, Christine Gaucher, Jean-François Prost, André Pèlegrin, Isabelle Navarro-Teulon
Ovarian cancer is the leading cause of death in women with gynecological cancers and despite recent advances, new and more efficient therapies are crucially needed. Müllerian Inhibiting Substance type II Receptor (MISRII, also named AMHRII) is expressed in most ovarian cancer subtypes and is a novel potential target for ovarian cancer immunotherapy. We previously developed and tested 12G4, the first murine monoclonal antibody (MAb) against human MISRII. Here, we report the humanization, affinity maturation and glyco-engineering steps of 12G4 to generate the Fc-optimized 3C23K MAb, and the evaluation of its in vivo anti-tumor activity...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425844/the-role-of-glucose-6-phosphate-dehydrogenase-in-adipose-tissue-inflammation-in-obesity
#5
Yoon Jeong Park, Sung Sik Choe, Jee Hyung Sohn, Jae Bum Kim
Obesity is closely associated with metabolic diseases including type 2 diabetes. One hallmark characteristics of obesity is chronic inflammation that is coordinately controlled by complex signaling networks in adipose tissues. Compelling evidence indicates that reactive oxygen species (ROS) and its related signaling pathways play crucial roles in the progression of chronic inflammation in obesity. The pentose phosphate pathway (PPP) is an anabolic pathway that utilizes the glucoses to generate molecular building blocks and reducing equivalents in the form of NADPH...
February 8, 2017: Adipocyte
https://www.readbyqxmd.com/read/28424239/aim2-inflammasome-is-critical-for-influenza-induced-lung-injury-and-mortality
#6
Hongbo Zhang, Jiadi Luo, John F Alcorn, Kong Chen, Songqing Fan, Joseph Pilewski, Aizhong Liu, Wei Chen, Jay K Kolls, Jieru Wang
The absent in melanoma 2 (AIM2) inflammasome plays an important role in many viral and bacterial infections, but very little is known about its role in RNA virus infection, including influenza A virus (IAV). In this study, we have designed in vivo and in vitro studies to determine the role of AIM2 in infections with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase-1 activation and release of cleaved IL-1β in the lung, which was significantly reduced in AIM2-deficient mice...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28422570/an-induced-adipocyte-sheet-reduces-inflammatory-reactions-during-remodeling-of-xenogeneic-scaffolds-in-vivo
#7
Tong Yi, Qiang Wang, Fan Fan, Gouhui Fan
Surgical therapy of cardiovascular diseases frequently requires replacement of diseased tissues with prosthetic devices or grafts. Calcification is the main reason for the degeneration of implanted grafts. However, some factors reduce stenosis and attenuate calcification of implanted grafts. In this study, we used an autologous induced adipocyte cell-sheet (IACS) as a drug delivery system to determine whether its secretion ability has a beneficial effect on the remodeling process of grafts in a rat subcutaneous model...
April 19, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28422079/synthetic-fluororutaecarpine-inhibits-inflammatory-stimuli-and-activates-endothelial-transient-receptor-potential-vanilloid-type-1
#8
Chi-Ming Lee, Jiun-An Gu, Tin-Gan Rau, Chi Wang, Chiao-Han Yen, Shih-Hao Huang, Feng-Yen Lin, Chun-Mao Lin, Sheng-Tung Huang
The natural product, rutaecarpine (RUT), is the main effective component of Evodia rutaecarpa which is a widely used traditional Chinese medicine. It has vasodilation, anticoagulation, and anti-inflammatory activities. However, further therapeutic applications are limited by its cytotoxicity. Thus, a derivative of RUT, 10-fluoro-2-methoxyrutaecarpine (F-RUT), was designed and synthesized that showed no cytotoxicity toward RAW264.7 macrophages at 20 μM. In an anti-inflammation experiment, it inhibited the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated RAW264...
April 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28421996/obesity-does-not-diminish-the-efficacy-of-il-6-signalling-blockade-in-mice-with-collagen-induced-arthritis
#9
Miho Suzuki, Keisuke Tanaka, Hiroto Yoshida, Kenji Yogo, Yoshihiro Matsumoto
OBJECTIVES: Obese rheumatoid arthritis patients often have higher disease activity and a poorer response to treatment than do non-obese patients. The present study aims to clarify the influence of obesity on the action of IL-6 and to evaluate the efficacy of IL-6 signalling blockade in arthritis with obesity. METHODS: Mice were fed a high-fat diet for 5 weeks, and the influence of this diet on macrophages and type II collagen-induced arthritis was investigated. RESULTS: The mice fed the high-fat diet showed greater expression of macrophage marker F4/80, not only in subcutaneous fat but also in knee synovium and the calcaneal region, than did the mice fed a normal diet...
April 18, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28421819/il-4-induces-the-il17rb-gene-transcription-in-monocytic-cells-with-coordinate-autocrine-il-25-signaling
#10
Nathaniel M Weathington, Shreya S Kanth, Qiaoke Gong, James Londino, Akihiko Hoji, Mauricio Rojas, John Trudeau, Sally Wenzel, Rama K Mallampalli
IL-25 and IL-4 signaling in the setting of infection or allergic responses can drive Type 2 inflammation. IL-25 requires the IL-17 receptor B (IL-17Rb) to mediate signaling through nuclear factor kappa B transcriptional activation. Despite the known coexistence of these two cytokines in the Type 2 inflammatory environment, collaborative signaling between the IL-4 and IL-25 axes is poorly explored. Here we demonstrate IL-4 induction of both IL-25 and IL-17Rb protein in human lung tissue culture, primary alveolar macrophages, and the THP-1 monocytic cell line...
April 19, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28420825/colchicine-improves-survival-left-ventricular-remodeling-and-chronic-cardiac-function-after-acute-myocardial-infarction
#11
Koichiro Fujisue, Koichi Sugamura, Hirofumi Kurokawa, Junichi Matsubara, Masanobu Ishii, Yasuhiro Izumiya, Koichi Kaikita, Seigo Sugiyama
BACKGROUND: Several studies have reported that colchicine attenuated the infarct size and inflammation in acute myocardial infarction (MI). However, the sustained benefit of colchicine administration on survival and cardiac function after MI is unknown. It was hypothesized that the short-term treatment with colchicine could improve survival and cardiac function during the recovery phase of MI.Methods and Results:MI was induced in mice by permanent ligation of the left anterior descending coronary artery...
April 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28420094/nonalcoholic-fatty-liver-disease-and-insulin-resistance-new-insights-and-potential-new-treatments
#12
REVIEW
Hironori Kitade, Guanliang Chen, Yinhua Ni, Tsuguhito Ota
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood...
April 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28417590/calcitonin-gene-related-peptide-cgrp-a-novel-target-for-alzheimer-s-disease
#13
REVIEW
Yogendra Singh, Gaurav Gupta, Birendra Shrivastava, Rajiv Dahiya, Juhi Tiwari, Madhu Ashwathanarayana, Rakesh Kumar Sharma, Mohit Agrawal, Anurag Mishra, Kamal Dua
Alzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid-β (Aβ) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene-related peptide (CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor-stimulating peptide...
April 17, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28414075/vitamin-b2-deficiency-enhances-the-pro-inflammatory-activity-of-adipocyte-consequences-for-insulin-resistance-and-metabolic-syndrome-development
#14
Agnieszka Irena Mazur-Bialy, Ewa Pocheć
AIMS: Adipose tissue is an endocrine organ important for regulation of such physiological processes as energy metabolism or lipids homeostasis. In an obesity state, it participates in the induction of chronic systemic inflammation accompanied by pro-inflammatory cytokines and fatty acid elevation. For this reasons, adipose tissue is involved in, e.g., insulin resistance, type 2 diabetes or hyperlipidemia development. In our previous study, we have shown that riboflavin deficiency induces a pathological pro-inflammatory response of macrophages, the main component of adipose tissue...
April 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28413316/ginsenoside-rc-from-panax-ginseng-exerts-anti-inflammatory-activity-by-targeting-tank-binding-kinase-1-interferon-regulatory-factor-3-and-p38-atf-2
#15
Tao Yu, Yanyan Yang, Yi-Seong Kwak, Gwan Gyu Song, Mi-Yeon Kim, Man Hee Rhee, Jae Youl Cho
BACKGROUND: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. METHODS: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis factor-α/interferon-γ-treated synovial cells, and HEK293 cells transfected with various inducers of inflammation...
April 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28413030/the-role-matrix-metalloproteinases-in-the-production-of-aortic-aneurysm
#16
Simon W Rabkin
Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of aortic aneurysm because the histology of thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) is characterized by the loss of smooth muscle cells in the aortic media and the destruction of extracellular matrix (ECM). Furthermore, AAA have evidence of inflammation and the cellular elements involved in inflammation such as macrophages can produce and/or activate MMPs This chapter focuses on human aortic aneurysm that are not due to specific known genetic causes because this type of aneurysm is the more common type...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28411252/prognostic-relevance-of-cd163-and-cd8-combined-with-ezh2-and-gain-of-chromosome-18-in-follicular-lymphoma-a-study-by-the-lunenburg-lymphoma-biomarker-consortium
#17
Wendy B C Stevens, Matias Mendeville, Robert Redd, Andrew J Clear, Reno Bladergroen, Maria Calaminici, Andreas Rosenwald, Eva Hoster, Wolfgang Hiddemann, Philippe Gaulard, Luc Xerri, Gilles Salles, Wolfram Klapper, Michael Phreundschuh, Andrew Jack, Randy D Gascoyne, Yasodha Natkunam, Ranjana Advani, Eva Kimby, Birgitta Sander, Laurie Sehn, Anton Hagenbeek, John Raemaekers, John Gribben, Marie Jose' Kersten, Bauke Ylstra, Edie Weller, Daphne de Jong
In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end-of-spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries; early failure: progression or lymphoma-related death <2 years versus long remission: response duration of >5 years...
April 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28410469/18%C3%AE-glycyrrhetinic-acid-the-major-bioactive-component-of-glycyrrhizae-radix-attenuates-airway-inflammation-by-modulating-th2-cytokines-gata-3-stat6-and-foxp3-transcription-factors-in-an-asthmatic-mouse-model
#18
Seung-Hyung Kim, Jung-Hee Hong, Ji-Eun Lee, Young-Cheol Lee
18β-Glycyrrhetinic acid (18Gly), the major bioactive component of Glycyrrhizae Radix, possesses anti-ulcerative, anti-inflammatory, and other pharmacological properties. Although 18Gly is associated with immunoregulatory functions of allergic diseases, the pathophysiological mechanisms of 18Gly action in allergic inflammatory lung disease have not been examined. Moreover, there are no in vivo studies on the anti-asthmatic effects of 18Gly in allergic asthma. We investigated its effect and mechanism of action in airway inflammation in a BALB/c mouse model of allergic asthma...
March 20, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28410407/bacterial-amyloid-curli-acts-as-a-carrier-for-dna-to-elicit-an-autoimmune-response-via-tlr2-and-tlr9
#19
Sarah A Tursi, Ernest Y Lee, Nicole J Medeiros, Michael H Lee, Lauren K Nicastro, Bettina Buttaro, Stefania Gallucci, Ronald Paul Wilson, Gerard C L Wong, Çagla Tükel
Bacterial biofilms are associated with numerous human infections. The predominant protein expressed in enteric biofilms is the amyloid curli, which forms highly immunogenic complexes with DNA. Infection with curli-expressing bacteria or systemic exposure to purified curli-DNA complexes triggers autoimmunity via the generation of type I interferons (IFNs) and anti-double-stranded DNA antibodies. Here, we show that DNA complexed with amyloid curli powerfully stimulates Toll-like receptor 9 (TLR9) through a two-step mechanism...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28410274/three-hypothetical-inflammation-pathobiology-phenotypes-and-pediatric-sepsis-induced-multiple-organ-failure-outcome
#20
Joseph A Carcillo, E Scott Halstead, Mark W Hall, Trung C Nguyen, Ron Reeder, Rajesh Aneja, Bita Shakoory, Dennis Simon
OBJECTIVES: We hypothesize that three inflammation pathobiology phenotypes are associated with increased inflammation, proclivity to develop features of macrophage activation syndrome, and multiple organ failure-related death in pediatric severe sepsis. DESIGN: Prospective cohort study comparing children with severe sepsis and any of three phenotypes: 1) immunoparalysis-associated multiple organ failure (whole blood ex vivo tumor necrosis factor response to endotoxin < 200 pg/mL), 2) thrombocytopenia-associated multiple organ failure (new onset thrombocytopenia with acute kidney injury and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 activity < 57%), and/or 3) sequential multiple organ failure with hepatobiliary dysfunction (respiratory distress followed by liver dysfunction with soluble Fas ligand > 200 pg/mL), to those without any of these phenotypes...
April 13, 2017: Pediatric Critical Care Medicine
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